Scholars@Duke
Joseph Heitman

Joseph Heitman

Chair, Department of Molecular Genetics and Microbiology
Molecular Genetics and Microbiology
heitm001@duke.edu
Duke Box 3546, Durham, NC 27710
322 Clin & Res Labs, Durham, NC 27710

Selected Publications

Distinct evolutionary trajectories following loss of RNA interference in Cryptococcus neoformans.

Journal Article Proc Natl Acad Sci U S A · November 19, 2024 While increased mutation rates typically have negative consequences in multicellular organisms, hypermutation can be advantageous for microbes adapting to the environment. Previously, we identified two hypermutator Cryptococcus neoformans clinical isolates ... Full text Link to item Cite

The Cryptococcus neoformans STRIPAK complex controls genome stability, sexual development, and virulence.

Journal Article PLoS Pathog · November 2024 The eukaryotic serine/threonine protein phosphatase PP2A is a heterotrimeric enzyme composed of a scaffold A subunit, a regulatory B subunit, and a catalytic C subunit. Of the four known B subunits, the B"' subunit (known as striatin) interacts with the mu ... Full text Link to item Cite

Malassezia responds to environmental pH signals through the conserved Rim/Pal pathway.

Journal Article mBio · October 16, 2024 During mammalian colonization and infection, microorganisms must be able to rapidly sense and adapt to changing environmental conditions including alterations in extracellular pH. The fungus-specific Rim/Pal signaling pathway is one process that supports m ... Full text Link to item Cite

Focus on fungi.

Journal Article Cell · September 19, 2024 Fungi play critical roles in the homeostasis of ecosystems globally and have emerged as significant causes of an expanding repertoire of devastating diseases in plants, animals, and humans. In this Commentary, we highlight the importance of fungal pathogen ... Full text Link to item Cite

Alternative ergosterol biosynthetic pathways confer antifungal drug resistance in the human pathogens within the Mucor species complex.

Journal Article mBio · August 14, 2024 UNLABELLED: Mucormycoses are emerging fungal infections caused by a variety of heterogeneous species within the Mucorales order. Among the Mucor species complex, Mucor circinelloides is the most frequently isolated pathogen in mucormycosis patients and des ... Full text Link to item Cite

Duplication and neofunctionalization of a horizontally transferred xyloglucanase as a facet of the Red Queen coevolutionary dynamic.

Journal Article Proc Natl Acad Sci U S A · June 11, 2024 Oomycete protists share phenotypic similarities with fungi, including the ability to cause plant diseases, but branch in a distant region of the tree of life. It has been suggested that multiple horizontal gene transfers (HGTs) from fungi-to-oomycetes cont ... Full text Link to item Cite

Alternative ergosterol biosynthetic pathways confer antifungal drug resistance in the human pathogens within the Mucor species complex.

Journal Article bioRxiv · June 1, 2024 Mucormycoses are emerging fungal infections caused by a variety of heterogeneous species within the Mucorales order. Among the Mucor species complex, Mucor circinelloides is the most frequently isolated pathogen in mucormycosis patients and despite its cli ... Full text Link to item Cite

Comparative genomics of the closely related fungal genera Cryptococcus and Kwoniella reveals karyotype dynamics and suggests evolutionary mechanisms of pathogenesis.

Journal Article PLoS Biol · June 2024 In exploring the evolutionary trajectories of both pathogenesis and karyotype dynamics in fungi, we conducted a large-scale comparative genomic analysis spanning the Cryptococcus genus, encompassing both global human fungal pathogens and nonpathogenic spec ... Full text Open Access Link to item Cite

Calcineurin contributes to RNAi-mediated transgene silencing and small interfering RNA production in the human fungal pathogen Cryptococcus neoformans.

Journal Article Genetics · March 6, 2024 Adaptation to external environmental challenges at the cellular level requires rapid responses and involves relay of information to the nucleus to drive key gene expression changes through downstream transcription factors. Here, we describe an alternative ... Full text Link to item Cite

Casein kinase 2 complex: a central regulator of multiple pathobiological signaling pathways in Cryptococcus neoformans.

Journal Article mBio · February 14, 2024 The casein kinase 2 (CK2) complex has garnered extensive attention over the past decades as a potential therapeutic target for diverse human diseases, including cancer, diabetes, and obesity, due to its pivotal roles in eukaryotic growth, differentiation, ... Full text Link to item Cite

Amoeba predation of Cryptococcus: A quantitative and population genomic evaluation of the accidental pathogen hypothesis.

Journal Article PLoS Pathog · November 2023 The "Amoeboid Predator-Fungal Animal Virulence Hypothesis" posits that interactions with environmental phagocytes shape the evolution of virulence traits in fungal pathogens. In this hypothesis, selection to avoid predation by amoeba inadvertently selects ... Full text Link to item Cite

Enhanced fungal specificity and in vivo therapeutic efficacy of a C-22-modified FK520 analog against C. neoformans.

Journal Article mBio · October 31, 2023 Fungal infections cause significant morbidity and mortality globally. The therapeutic armamentarium against these infections is limited, and the development of antifungal drugs has been hindered by the evolutionary conservation between fungi and the human ... Full text Link to item Cite

Duplication and neofunctionalization of a horizontally-transferred xyloglucanase as a facet of the red queen co-evolutionary dynamic.

Journal Article bioRxiv · October 9, 2023 UNLABELLED: Oomycetes are heterotrophic protists that share phenotypic similarities with fungi, including the ability to cause plant diseases, but branch in a separate and distant region of the eukaryotic tree of life. It has been suggested that multiple h ... Full text Link to item Cite

Frequent transitions in mating-type locus chromosomal organization in Malassezia and early steps in sexual reproduction.

Journal Article Proc Natl Acad Sci U S A · August 8, 2023 Fungi in the basidiomycete genus Malassezia are the most prevalent eukaryotic microbes resident on the skin of human and other warm-blooded animals and have been implicated in skin diseases and systemic disorders. Analysis of Malassezia genomes revealed th ... Full text Link to item Cite

Sequencing the Genomes of the First Terrestrial Fungal Lineages: What Have We Learned?

Journal Article Microorganisms · July 18, 2023 The first genome sequenced of a eukaryotic organism was for Saccharomyces cerevisiae, as reported in 1996, but it was more than 10 years before any of the zygomycete fungi, which are the early-diverging terrestrial fungi currently placed in the phyla Mucor ... Full text Link to item Cite

Enhanced fungal specificity and in vivo therapeutic efficacy of a C-22 modified FK520 analog against C. neoformans.

Journal Article bioRxiv · July 11, 2023 UNLABELLED: Fungal infections are of mounting global concern, and the current limited treatment arsenal poses challenges when treating such infections. In particular, infections by Cryptococcus neoformans are associated with high mortality, emphasizing the ... Full text Link to item Cite

Frequent transitions in mating-type locus chromosomal organization in Malassezia and early steps in sexual reproduction.

Journal Article bioRxiv · June 9, 2023 UNLABELLED: Fungi in the basidiomycete genus Malassezia are the most prevalent eukaryotic microbes resident on the skin of human and other warm-blooded animals and have been implicated in skin diseases and systemic disorders. Analysis of Malassezia genomes ... Full text Link to item Cite

On the evolution of variation in sexual reproduction through the prism of eukaryotic microbes.

Journal Article Proc Natl Acad Sci U S A · March 7, 2023 Almost all eukaryotes undergo sexual reproduction to generate diversity and select for fitness in their population pools. Interestingly, the systems by which sex is defined are highly diverse and can even differ between evolutionarily closely related speci ... Full text Link to item Cite

Heterochromatin and RNAi act independently to ensure genome stability in Mucorales human fungal pathogens.

Journal Article Proc Natl Acad Sci U S A · February 14, 2023 Chromatin modifications play a fundamental role in controlling transcription and genome stability and yet despite their importance, are poorly understood in early-diverging fungi. We present a comprehensive study of histone lysine and DNA methyltransferase ... Full text Link to item Cite

Genome-wide analysis of heat stress-stimulated transposon mobility in the human fungal pathogen Cryptococcus deneoformans.

Journal Article Proc Natl Acad Sci U S A · January 24, 2023 We recently reported transposon mutagenesis as a significant driver of spontaneous mutations in the human fungal pathogen Cryptococcus deneoformans during murine infection. Mutations caused by transposable element (TE) insertion into reporter genes were dr ... Full text Link to item Cite

Lessons learned: from mentored to mentor.

Journal Article J Clin Invest · January 17, 2023 This Viewpoint was written in association with the 25th anniversary of the American Society for Clinical Investigation's (ASCI's) Stanley J. Korsmeyer Award, which honors the highest standards of scientific excellence, meritorious research, intellectual in ... Full text Link to item Cite

Drug Target Elucidation Through Isolation and Analysis of Drug-Resistant Mutants in Cryptococcus neoformans.

Journal Article Methods Mol Biol · 2023 Drug target identification is an essential component to antifungal drug development. Many methods, including large chemical library screening, natural product screening, and drug repurposing efforts, can identify compounds with favorable in vitro antifunga ... Full text Link to item Cite

The IV International Symposium on Fungal Stress and the XIII International Fungal Biology Conference.

Conference Fungal Biol · 2023 For the first time, the International Symposium on Fungal Stress was joined by the XIII International Fungal Biology Conference. The International Symposium on Fungal Stress (ISFUS), always held in Brazil, is now in its fourth edition, as an event of recog ... Full text Link to item Cite

Unraveling the Pathobiological Role of the Fungal KEOPS Complex in Cryptococcus neoformans.

Journal Article mBio · December 20, 2022 The KEOPS (kinase, putative endopeptidase, and other proteins of small size) complex has critical functions in eukaryotes; however, its role in fungal pathogens remains elusive. Herein, we comprehensively analyzed the pathobiological functions of the funga ... Full text Link to item Cite

The future of fungi: threats and opportunities.

Journal Article G3 (Bethesda) · November 4, 2022 The fungal kingdom represents an extraordinary diversity of organisms with profound impacts across animal, plant, and ecosystem health. Fungi simultaneously support life, by forming beneficial symbioses with plants and producing life-saving medicines, and ... Full text Link to item Cite

Uncontrolled transposition following RNAi loss causes hypermutation and antifungal drug resistance in clinical isolates of Cryptococcus neoformans.

Journal Article Nat Microbiol · August 2022 Cryptococcus neoformans infections cause approximately 15% of AIDS-related deaths owing to a combination of limited antifungal therapies and drug resistance. A collection of clinical and environmental C. neoformans isolates were assayed for increased mutat ... Full text Link to item Cite

Infection and inflammation: New perspectives on Alzheimer's disease.

Journal Article Brain Behav Immun Health · July 2022 Neuroinflammation has been recognized as a component of Alzheimer's Disease (AD) pathology since the original descriptions by Alois Alzheimer and a role for infections in AD pathogenesis has long been hypothesized. More recently, this hypothesis has gained ... Full text Link to item Cite

On Fruits and Fungi: A Risk of Antifungal Usage in Food Storage and Distribution in Driving Drug Resistance in Candida auris.

Journal Article mBio · June 28, 2022 The continuous emergence of antifungal drug resistance is a mounting concern for the treatment of fungal infections worldwide. While many pathogenic fungi exhibit some level of antifungal drug resistance, the identification of Candida auris has brought thi ... Full text Link to item Cite

Structure-Guided Synthesis of FK506 and FK520 Analogs with Increased Selectivity Exhibit In Vivo Therapeutic Efficacy against Cryptococcus.

Journal Article mBio · June 28, 2022 Calcineurin is an essential virulence factor that is conserved across human fungal pathogens, including Cryptococcus neoformans, Aspergillus fumigatus, and Candida albicans. Although an excellent target for antifungal drug development, the serine-threonine ... Full text Open Access Link to item Cite

Obligate sexual reproduction of a homothallic fungus closely related to the Cryptococcus pathogenic species complex.

Journal Article Elife · June 17, 2022 eLife digest. Fungi are enigmatic organisms that flourish in soil, on decaying plants, or during infection of animals or plants. Growing in myriad forms, from single-celled yeast to multicellular molds and mushrooms, fungi have also evolved ... Full text Link to item Cite

Exploring Space via Astromycology: A Report on the CIFAR Programs Earth 4D and Fungal Kingdom Inaugural Joint Meeting.

Journal Article Astrobiology · June 2022 "Fungi on Mars!": a popular news heading that piques public interest and makes scientists' blood boil. While such a statement is laden with misinformation and light on evidence, the search for past and present extraterrestrial life is an ongoing scientific ... Full text Link to item Cite

Multiple Hybridization Events Punctuate the Evolutionary Trajectory of Malassezia furfur.

Journal Article mBio · April 26, 2022 Malassezia species are important fungal skin commensals and are part of the normal microbiota of humans and other animals. However, under certain circumstances these fungi can also display a pathogenic behavior. For example, Malassezia furfur is a common c ... Full text Link to item Cite

Identification of Mucormycosis by Fluorescence In Situ Hybridization Targeting Ribosomal RNA in Tissue Samples.

Journal Article J Fungi (Basel) · March 11, 2022 Mucormycosis is an invasive fungal infection associated with high mortality, partly due to delayed diagnosis and inadequate empiric therapy. As fungal cultures often fail to grow Mucorales, identification of respective hyphae in tissue is frequently needed ... Full text Link to item Cite

Epistatic genetic interactions govern morphogenesis during sexual reproduction and infection in a global human fungal pathogen.

Journal Article Proc Natl Acad Sci U S A · February 22, 2022 Cellular development is orchestrated by evolutionarily conserved signaling pathways, which are often pleiotropic and involve intra- and interpathway epistatic interactions that form intricate, complex regulatory networks. Cryptococcus species are a group o ... Full text Link to item Cite

Joseph Heitman.

Journal Article Curr Biol · February 7, 2022 Interview with Joseph Heitman, who studies model and pathogenic fungi at Duke University Medical Center. ... Full text Open Access Link to item Cite

Clonal evolution in serially passaged Cryptococcus neoformans × deneoformans hybrids reveals a heterogenous landscape of genomic change.

Journal Article Genetics · January 4, 2022 Cryptococcus neoformans × deneoformans hybrids (also known as serotype AD hybrids) are basidiomycete yeasts that are common in a clinical setting. Like many hybrids, the AD hybrids are largely locked at the F1 stage and are mostly unable to undergo normal ... Full text Link to item Cite

Leveraging Fungal and Human Calcineurin-Inhibitor Structures, Biophysical Data, and Dynamics To Design Selective and Nonimmunosuppressive FK506 Analogs.

Journal Article mBio · December 21, 2021 Calcineurin is a critical enzyme in fungal pathogenesis and antifungal drug tolerance and, therefore, an attractive antifungal target. Current clinically accessible calcineurin inhibitors, such as FK506, are immunosuppressive to humans, so exploiting calci ... Full text Open Access Link to item Cite

Dynamic genome plasticity during unisexual reproduction in the human fungal pathogen Cryptococcus deneoformans.

Journal Article PLoS Genet · November 2021 Genome copy number variation occurs during each mitotic and meiotic cycle and it is crucial for organisms to maintain their natural ploidy. Defects in ploidy transitions can lead to chromosome instability, which is a hallmark of cancer. Ploidy in the haplo ... Full text Link to item Cite

Uniparental nuclear inheritance following bisexual mating in fungi.

Journal Article Elife · August 2, 2021 Some remarkable animal species require an opposite-sex partner for their sexual development but discard the partner's genome before gamete formation, generating hemi-clonal progeny in a process called hybridogenesis. Here, we discovered a similar phenomeno ... Full text Link to item Cite

Epigenetic dynamics of centromeres and neocentromeres in Cryptococcus deuterogattii.

Journal Article PLoS Genet · August 2021 Deletion of native centromeres in the human fungal pathogen Cryptococcus deuterogattii leads to neocentromere formation. Native centromeres span truncated transposable elements, while neocentromeres do not and instead span actively expressed genes. To expl ... Full text Link to item Cite

Correction to: The evolving species concepts used for yeasts: from phenotypes and genomes to speciation networks (Fungal Diversity, (2021), 109, 1, (27-55), 10.1007/s13225-021-00475-9)

Journal Article Fungal Diversity · July 1, 2021 The name of the second author was incorrectly captured in the initial online publication, and due to an error at the proofs stage, several proof corrections had been left undone. The original online article has been corrected. ... Full text Cite

Molecular Tools for the Yeast Papiliotrema terrestris LS28 and Identification of Yap1 as a Transcription Factor Involved in Biocontrol Activity.

Journal Article Appl Environ Microbiol · March 11, 2021 Fungal attacks on stored fruit and vegetables are responsible for losses of products. There is an active research field to develop alternative strategies for postharvest disease management, and the use of biocontrol agents represents a promising approach. ... Full text Link to item Cite

Multiple Pathways to Homothallism in Closely Related Yeast Lineages in the Basidiomycota.

Journal Article mBio · February 16, 2021 Sexual reproduction in fungi relies on proteins with well-known functions encoded by the mating type (MAT) loci. In the Basidiomycota, MAT loci are often bipartite, with the P/R locus encoding pheromone precursors and pheromone receptors and the HD locus e ... Full text Link to item Cite

Application of an optimized annotation pipeline to the Cryptococcus deuterogattii genome reveals dynamic primary metabolic gene clusters and genomic impact of RNAi loss.

Journal Article G3 (Bethesda) · February 9, 2021 Evaluating the quality of a de novo annotation of a complex fungal genome based on RNA-seq data remains a challenge. In this study, we sequentially optimized a Cufflinks-CodingQuary-based bioinformatics pipeline fed with RNA-seq data using the manually ann ... Full text Link to item Cite

Factors enforcing the species boundary between the human pathogens Cryptococcus neoformans and Cryptococcus deneoformans.

Journal Article PLoS Genet · January 2021 Hybridization has resulted in the origin and variation in extant species, and hybrids continue to arise despite pre- and post-zygotic barriers that limit their formation and evolutionary success. One important system that maintains species boundaries in pr ... Full text Link to item Cite

Pleiotropy and epistasis within and between signaling pathways defines the genetic architecture of fungal virulence.

Journal Article PLoS Genet · January 2021 Cryptococcal disease is estimated to affect nearly a quarter of a million people annually. Environmental isolates of Cryptococcus deneoformans, which make up 15 to 30% of clinical infections in temperate climates such as Europe, vary in their pathogenicity ... Full text Link to item Cite

The evolving species concepts used for yeasts: from phenotypes and genomes to speciation networks.

Journal Article Fungal Divers · 2021 Here we review how evolving species concepts have been applied to understand yeast diversity. Initially, a phenotypic species concept was utilized taking into consideration morphological aspects of colonies and cells, and growth profiles. Later the biologi ... Full text Link to item Cite

A Novel Virus Alters Gene Expression and Vacuolar Morphology in Malassezia Cells and Induces a TLR3-Mediated Inflammatory Immune Response

Journal Article mBio · October 27, 2020 Malassezia is the most dominant fungal genus on the human skin surface and is associated with various skin diseases including dandruff and seborrheic dermatitis. Among Mal ... Full text Cite

The Untapped Australasian Diversity of Astaxanthin-Producing Yeasts with Biotechnological Potential-Phaffia australis sp. nov. and Phaffia tasmanica sp. nov.

Journal Article Microorganisms · October 24, 2020 Phaffia is an orange-colored basidiomycetous yeast genus of the order Cystofilobasidiales that contains a single species, P. rhodozyma. This species is the only fungus known to produce the economically relevant carotenoid astaxanthin. Although Phaffia was ... Full text Link to item Cite

Fungal pathogens.

Journal Article Curr Biol · October 5, 2020 Fungi are key components in global biogeochemical cycles, play important roles in manufacturing industries and biomedical research, and influence humans through their impact on global health, agriculture, and biodiversity. Fungi have been isolated from alm ... Full text Link to item Cite

A Novel Mycovirus Evokes Transcriptional Rewiring in the Fungus Malassezia and Stimulates Beta Interferon Production in Macrophages.

Journal Article mBio · September 1, 2020 Mycoviruses infect fungi, and while most persist asymptomatically, there are examples of mycoviruses having both beneficial and detrimental effects on their host. Virus-infected Saccharomyces and Ustilago strains exhibit a killer phenotype conferring a gro ... Full text Link to item Cite

Microbe Profile: Cryptococcus neoformans species complex.

Journal Article Microbiology (Reading) · September 2020 Cryptococcus neoformans is a lethal fungus disguised in a polysaccharide coat. It can remain dormant in the host for decades prior to reactivation, causing systemic cryptococcosis in humans and other mammals. Cryptococcus deploys a multitude of traits to a ... Full text Link to item Cite

Genome-wide functional analysis of phosphatases in the pathogenic fungus Cryptococcus neoformans.

Journal Article Nat Commun · August 24, 2020 Phosphatases, together with kinases and transcription factors, are key components in cellular signalling networks. Here, we present a systematic functional analysis of the phosphatases in Cryptococcus neoformans, a fungal pathogen that causes life-threaten ... Full text Link to item Cite

The necessity for molecular classification of basidiomycetous biocontrol yeasts

Journal Article BioControl · August 1, 2020 The field of plant protection is steadily reducing the use of chemicals by increasing the use of microbial biocontrol agents. At present, several microorganisms are active ingredients of the so-called biofungicides and some of these are based on yeasts. Mo ... Full text Cite

HGT in the human and skin commensal Malassezia: A bacterially derived flavohemoglobin is required for NO resistance and host interaction.

Journal Article Proc Natl Acad Sci U S A · July 7, 2020 The skin of humans and animals is colonized by commensal and pathogenic fungi and bacteria that share this ecological niche and have established microbial interactions. Malassezia are the most abundant fungal skin inhabitant of warm-blooded animals and hav ... Full text Open Access Link to item Cite

Tornadic Shear Stress Induces a Transient, Calcineurin-Dependent Hypervirulent Phenotype in Mucorales Molds.

Journal Article mBio · June 30, 2020 Trauma-related necrotizing myocutaneous mucormycosis (NMM) has a high morbidity and mortality in victims of combat-related injuries, geometeorological disasters, and severe burns. Inspired by the observation that several recent clusters of NMM have been as ... Full text Link to item Cite

The Rise of Fungi: A Report on the CIFAR Program Fungal Kingdom: Threats & Opportunities Inaugural Meeting.

Journal Article G3 (Bethesda) · June 1, 2020 The first meeting of the CIFAR Fungal Kingdom: Threats & Opportunities research program saw the congregation of experts on fungal biology to address the most pressing threats fungi pose to global health, agriculture, and biodiversity. This report covers th ... Full text Link to item Cite

FKBP12 dimerization mutations effect FK506 binding and differentially alter calcineurin inhibition in the human pathogen Aspergillus fumigatus.

Journal Article Biochem Biophys Res Commun · May 21, 2020 The 12-kDa FK506-binding protein (FKBP12) is the target of the commonly used immunosuppressive drug FK506. The FKBP12-FK506 complex binds to calcineurin and inhibits its activity, leading to immunosuppression and preventing organ transplant rejection. Our ... Full text Open Access Link to item Cite

Transposon mobilization in the human fungal pathogen Cryptococcus is mutagenic during infection and promotes drug resistance in vitro.

Journal Article Proc Natl Acad Sci U S A · May 5, 2020 When transitioning from the environment, pathogenic microorganisms must adapt rapidly to survive in hostile host conditions. This is especially true for environmental fungi that cause opportunistic infections in immunocompromised patients since these micro ... Full text Link to item Cite

Threats Posed by the Fungal Kingdom to Humans, Wildlife, and Agriculture.

Journal Article mBio · May 5, 2020 The fungal kingdom includes at least 6 million eukaryotic species and is remarkable with respect to its profound impact on global health, biodiversity, ecology, agriculture, manufacturing, and biomedical research. Approximately 625 fungal species have been ... Full text Link to item Cite

Centromere deletion in Cryptococcus deuterogattii leads to neocentromere formation and chromosome fusions.

Journal Article Elife · April 20, 2020 The human fungal pathogen Cryptococcus deuterogattii is RNAi-deficient and lacks active transposons in its genome. C. deuterogattii has regional centromeres that contain only transposon relics. To investigate the impact of centromere loss on the C. deutero ... Full text Link to item Cite

Centromere scission drives chromosome shuffling and reproductive isolation.

Journal Article Proc Natl Acad Sci U S A · April 7, 2020 A fundamental characteristic of eukaryotic organisms is the generation of genetic variation via sexual reproduction. Conversely, significant large-scale genome structure variations could hamper sexual reproduction, causing reproductive isolation and promot ... Full text Link to item Cite

Mating-Type-Specific Ribosomal Proteins Control Aspects of Sexual Reproduction in Cryptococcus neoformans.

Journal Article Genetics · March 2020 The MAT locus of Cryptococcus neoformans has a bipolar organization characterized by an unusually large structure, spanning over 100 kb. MAT genes have been characterized by functional genetics as being involved in sexual reproduction and virulence. Howeve ... Full text Link to item Cite

The Pheromone and Pheromone Receptor Mating-Type Locus Is Involved in Controlling Uniparental Mitochondrial Inheritance in Cryptococcus.

Journal Article Genetics · March 2020 Mitochondria are inherited uniparentally during sexual reproduction in the majority of eukaryotic species studied, including humans, mice, and nematodes, as well as many fungal species. Mitochondrial uniparental inheritance (mito-UPI) could be beneficial i ... Full text Link to item Cite

Long transposon-rich centromeres in an oomycete reveal divergence of centromere features in Stramenopila-Alveolata-Rhizaria lineages.

Journal Article PLoS Genet · March 2020 Centromeres are chromosomal regions that serve as platforms for kinetochore assembly and spindle attachments, ensuring accurate chromosome segregation during cell division. Despite functional conservation, centromere DNA sequences are diverse and often rep ... Full text Link to item Cite

She Loves Me, She Loves Me Not: On the Dualistic Asexual/Sexual Nature of Dermatophyte Fungi.

Journal Article Mycopathologia · February 2020 Dermatophytes are ascomycetous fungi whose sexuality is greatly influenced by their ecology. Sexual reproduction is ubiquitous among soil-related geophiles and some animal-associated zoophiles. In contrast, anthropophiles are generally present as a single ... Full text Link to item Cite

A Novel Resistance Pathway for Calcineurin Inhibitors in the Human-Pathogenic Mucorales Mucor circinelloides.

Journal Article mBio · January 28, 2020 Mucormycosis is an emerging lethal fungal infection in immunocompromised patients. Mucor circinelloides is a causal agent of mucormycosis and serves as a model system to understand genetics in Mucorales. Calcineurin is a conserved virulence factor in many ... Full text Link to item Cite

Loss of centromere function drives karyotype evolution in closely related Malassezia species.

Journal Article Elife · January 20, 2020 Genomic rearrangements associated with speciation often result in variation in chromosome number among closely related species. Malassezia species show variable karyotypes ranging between six and nine chromosomes. Here, we experimentally identified all eig ... Full text Link to item Cite

5-fluorocytosine resistance is associated with hypermutation and alterations in capsule biosynthesis in Cryptococcus.

Journal Article Nat Commun · January 8, 2020 Patients infected with the fungal pathogen Cryptococcus are most effectively treated with a combination of 5-fluorocytosine (5FC) and amphotericin B. 5FC acts as a prodrug, which is converted into toxic 5-fluorouracil (5FU) upon uptake into fungal cells. H ... Full text Link to item Cite

Transposon mobilization in the human fungal pathogenCryptococcus deneoformansis mutagenic during infection and promotes drug resistancein vitro

Journal Article · 2020 ABSTRACT When transitioning from the environment, pathogenic microorganisms must adapt rapidly to survive in hostile host conditions. This is especially true for environmental fungi that cause opportunistic infections in immunocompromised patients ... Full text Cite

Leveraging Fungal Calcineurin-Inhibitor Structures, Biophysics and Dynamics to Design Selective and Non-Immunosuppressive FK506 Analogs

Journal Article · 2020 Calcineurin is a critical enzyme in fungal pathogenesis and antifungal drug tolerance and, therefore, an attractive antifungal target. Current clinically-accessible calcineurin inhibitors, such as FK506, are immunosuppressive to humans, so exploiting calci ... Full text Open Access Cite

Advances in understanding the evolution of fungal genome architecture.

Journal Article F1000Res · 2020 Diversity within the fungal kingdom is evident from the wide range of morphologies fungi display as well as the various ecological roles and industrial purposes they serve. Technological advances, particularly in long-read sequencing, coupled with the incr ... Full text Link to item Cite

Expression of a Malassezia Codon Optimized mCherry Fluorescent Protein in a Bicistronic Vector.

Journal Article Front Cell Infect Microbiol · 2020 The use of fluorescent proteins allows a multitude of approaches from live imaging and fixed cells to labeling of whole organisms, making it a foundation of diverse experiments. Tagging a protein of interest or specific cell type allows visualization and s ... Full text Link to item Cite

Approaches for Genetic Discoveries in the Skin Commensal and Pathogenic Malassezia Yeasts.

Journal Article Front Cell Infect Microbiol · 2020 Malassezia includes yeasts belong to the subphylum Ustilaginomycotina within the Basidiomycota. Malassezia yeasts are commonly found as commensals on human and animal skin. Nevertheless, Malassezia species are also associated with several skin disorders, s ... Full text Link to item Cite

The Evolution of Sexual Reproduction and the Mating-Type Locus: Links to Pathogenesis of Cryptococcus Human Pathogenic Fungi.

Journal Article Annu Rev Genet · December 3, 2019 Cryptococcus species utilize a variety of sexual reproduction mechanisms, which generate genetic diversity, purge deleterious mutations, and contribute to their ability to occupy myriad environmental niches and exhibit a range of pathogenic potential. The ... Full text Link to item Cite

Early Diverging Fungus Mucor circinelloides Lacks Centromeric Histone CENP-A and Displays a Mosaic of Point and Regional Centromeres.

Journal Article Curr Biol · November 18, 2019 Centromeres are rapidly evolving across eukaryotes, despite performing a conserved function to ensure high-fidelity chromosome segregation. CENP-A chromatin is a hallmark of a functional centromere in most organisms. Due to its critical role in kinetochore ... Full text Link to item Cite

Drug-Resistant Epimutants Exhibit Organ-Specific Stability and Induction during Murine Infections Caused by the Human Fungal Pathogen Mucor circinelloides.

Journal Article mBio · November 5, 2019 The environmentally ubiquitous fungus Mucor circinelloides is a primary cause of the emerging disease mucormycosis. Mucor infection is notable for causing high morbidity and mortality, especially in immunosuppressed patients, while being inherently resista ... Full text Link to item Cite

Epigenetic mechanisms of drug resistance in fungi.

Journal Article Fungal Genet Biol · November 2019 The emergence of drug-resistant fungi poses a continuously increasing threat to human health. Despite advances in preventive care and diagnostics, resistant fungi continue to cause significant mortality, especially in immunocompromised patients. Therapeuti ... Full text Link to item Cite

Calcium-Calmodulin-Calcineurin Signaling: A Globally Conserved Virulence Cascade in Eukaryotic Microbial Pathogens.

Journal Article Cell Host Microbe · October 9, 2019 Calcium is an abundant intracellular ion, and calcium homeostasis plays crucial roles in several cellular processes. The calcineurin signaling cascade is one of the major pathways governed by intracellular calcium. Calcineurin, a conserved protein from yea ... Full text Link to item Cite

Genetic and genomic evolution of sexual reproduction: echoes from LECA to the fungal kingdom.

Journal Article Curr Opin Genet Dev · October 2019 Sexual reproduction is vastly diverse and yet highly conserved across the eukaryotic domain. This ubiquity suggests that the last eukaryotic common ancestor (LECA) was sexual. It is hypothesized that several critical processes in sexual reproduction, inclu ... Full text Link to item Cite

Harnessing calcineurin-FK506-FKBP12 crystal structures from invasive fungal pathogens to develop antifungal agents.

Journal Article Nat Commun · September 19, 2019 Calcineurin is important for fungal virulence and a potential antifungal target, but compounds targeting calcineurin, such as FK506, are immunosuppressive. Here we report the crystal structures of calcineurin catalytic (CnA) and regulatory (CnB) subunits c ... Full text Open Access Link to item Cite

E Pluribus Unum: The Fungal Kingdom as a Rosetta Stone for Biology and Medicine.

Journal Article Genetics · September 2019 THE Genetics Society of America's (GSA's) Edward Novitski Prize recognizes a single experimental accomplishment or a body of work in which an exceptional level of creativity, and intellectual ingenuity, has been used to design and execute scientific experi ... Full text Link to item Cite

Convergent evolution of linked mating-type loci in basidiomycete fungi.

Journal Article PLoS Genet · September 2019 Sexual development is a key evolutionary innovation of eukaryotes. In many species, mating involves interaction between compatible mating partners that can undergo cell and nuclear fusion and subsequent steps of development including meiosis. Mating compat ... Full text Link to item Cite

Unisexual reproduction promotes competition for mating partners in the global human fungal pathogen Cryptococcus deneoformans.

Journal Article PLoS Genet · September 2019 Courtship is pivotal for successful mating. However, courtship is challenging for the Cryptococcus neoformans species complex, comprised of opportunistic fungal pathogens, as the majority of isolates are α mating type. In the absence of mating partners of ... Full text Link to item Cite

Mating-System Evolution: All Roads Lead to Selfing.

Journal Article Curr Biol · August 5, 2019 Fungi reproduce via both heterothallic outcrossing and homothallic selfing modes, and transitions between the two are common throughout the tree of life. A new study reports that the transition from heterothallism to homothallism is common and has repeated ... Full text Link to item Cite

Advancing Functional Genetics Through Agrobacterium-Mediated Insertional Mutagenesis and CRISPR/Cas9 in the Commensal and Pathogenic Yeast Malassezia.

Journal Article Genetics · August 2019 Malassezia encompasses a monophyletic group of basidiomycetous yeasts naturally found on the skin of humans and other animals. Malassezia species have lost genes for lipid biosynthesis, and are therefore lipid-dependent and difficult to manipulate under la ... Full text Link to item Cite

Genetic and Genomic Analyses Reveal Boundaries between Species Closely Related to Cryptococcus Pathogens.

Journal Article mBio · June 11, 2019 Speciation is a central mechanism of biological diversification. While speciation is well studied in plants and animals, in comparison, relatively little is known about speciation in fungi. One fungal model is the Cryptococcus genus, which is best known fo ... Full text Link to item Cite

Gastrointestinal microbiota alteration induced by Mucor circinelloides in a murine model.

Conference J Microbiol · June 2019 Mucor circinelloides is a pathogenic fungus and etiologic agent of mucormycosis. In 2013, cases of gastrointestinal illness after yogurt consumption were reported to the US FDA, and the producer found that its products were contaminated with Mucor. A previ ... Full text Link to item Cite

Cryptococcus neoformans Mating and Genetic Crosses.

Journal Article Curr Protoc Microbiol · June 2019 The Cryptococcus pathogenic species complex is a group of opportunistic human fungal pathogens that cause cryptococcal meningoencephalitis, an infection associated with unacceptably high mortality rates. The public health relevance of these pathogens has g ... Full text Link to item Cite

Fungi in the Marine Environment: Open Questions and Unsolved Problems.

Journal Article mBio · March 5, 2019 Terrestrial fungi play critical roles in nutrient cycling and food webs and can shape macroorganism communities as parasites and mutualists. Although estimates for the number of fungal species on the planet range from 1.5 to over 5 million, likely fewer th ... Full text Link to item Cite

Mating type (MAT) locus and possible sexuality of the opportunistic pathogen Exophiala dermatitidis.

Journal Article Fungal Genet Biol · March 2019 Sexual reproduction among the black yeasts is generally limited to environmental saprobic species and is rarely observed among opportunists in humans. To date, a complete sexual cycle has not been observed in Exophiala dermatitidis. In this study, we aimed ... Full text Link to item Cite

Cryptococcus deuterogattii VGIIa Infection Associated with Travel to the Pacific Northwest Outbreak Region in an Anti-Granulocyte-Macrophage Colony-Stimulating Factor Autoantibody-Positive Patient in the United States.

Journal Article mBio · February 12, 2019 The region encompassing the Pacific Northwest (PNW), Vancouver Island, Oregon, and Washington has been the location of an ongoing Cryptococcus gattii outbreak since the 1990s, and there is evidence that the outbreak is expanding along the West Coast into C ... Full text Link to item Cite

Mucor circinelloides Thrives inside the Phagosome through an Atf-Mediated Germination Pathway.

Journal Article mBio · February 5, 2019 Mucormycosis is an emerging fungal infection that is often lethal due to the ineffectiveness of current therapies. Here, we have studied the first stage of this infection-the germination of Mucor circinelloides spores inside phagocytic cells-from an integr ... Full text Link to item Cite

Broad antifungal resistance mediated by RNAi-dependent epimutation in the basal human fungal pathogen Mucor circinelloides.

Journal Article PLoS Genet · February 2019 Mucormycosis-an emergent, deadly fungal infection-is difficult to treat, in part because the causative species demonstrate broad clinical antifungal resistance. However, the mechanisms underlying drug resistance in these infections remain poorly understood ... Full text Link to item Cite

Nutrient and Stress Sensing in Pathogenic Yeasts.

Journal Article Front Microbiol · 2019 More than 1.5 million fungal species are estimated to live in vastly different environmental niches. Despite each unique host environment, fungal cells sense certain fundamentally conserved elements, such as nutrients, pheromones and stress, for adaptation ... Full text Link to item Cite

Pbp1-Interacting Protein Mkt1 Regulates Virulence and Sexual Reproduction in Cryptococcus neoformans.

Journal Article Front Cell Infect Microbiol · 2019 The Mkt1-Pbp1 complex promotes mating-type switching by regulating the translation of HO mRNA in Saccharomyces cerevisiae. Here, we performed in vivo immunoprecipitation assays and mass spectrometry analyses in the human fungal pathogen Cryptococcus neofor ... Full text Open Access Link to item Cite

Cryptococcus neoformans Recovered From Olive Trees (Olea europaea) in Turkey Reveal Allopatry With African and South American Lineages.

Journal Article Front Cell Infect Microbiol · 2019 Cryptococcus species are life-threatening human fungal pathogens that cause cryptococcal meningoencephalitis in both immunocompromised and healthy hosts. The natural environmental niches of Cryptococcus include pigeon (Columba livia) guano, soil, and a var ... Full text Link to item Cite

In Vitro and In Vivo Assessment of FK506 Analogs as Novel Antifungal Drug Candidates.

Journal Article Antimicrob Agents Chemother · November 2018 FK506 (tacrolimus) is an FDA-approved immunosuppressant indicated for the prevention of allograft rejections in patients undergoing organ transplants. In mammals, FK506 inhibits the calcineurin-nuclear factor of activated T cells (NFAT) pathway to prevent ... Full text Link to item Cite

A High-Resolution Map of Meiotic Recombination in Cryptococcus deneoformans Demonstrates Decreased Recombination in Unisexual Reproduction.

Journal Article Genetics · June 2018 Multiple species within the basidiomycete genus Cryptococcus cause cryptococcal disease. These species are estimated to affect nearly a quarter of a million people leading to ∼180,000 mortalities, annually. Sexual reproduction, which can occur between hapl ... Full text Link to item Cite

Phylogenetic and Phylogenomic Definition of Rhizopus Species.

Journal Article G3 (Bethesda) · May 31, 2018 Phylogenomic approaches have the potential to improve confidence about the inter-relationships of species in the order Mucorales within the fungal tree of life. Rhizopus species are especially important as plant and animal pathogens and bioindustrial ferme ... Full text Link to item Cite

Evolutionarily Conserved and Divergent Roles of Unfolded Protein Response (UPR) in the Pathogenic Cryptococcus Species Complex.

Journal Article Sci Rep · May 25, 2018 The unfolded protein response (UPR) pathway, consisting of the evolutionarily conserved Ire1 kinase/endonuclease and the bZIP transcription factor Hxl1, is critical for the pathogenicity of Cryptococcus neoformans; however, its role remains unknown in othe ... Full text Link to item Cite

The Skin Commensal Yeast Malassezia globosa Thwarts Bacterial Biofilms to Benefit the Host.

Journal Article J Invest Dermatol · May 2018 Malassezia are abundant, lipid-dependent, commensal yeasts in the skin microbiome that also have a pathogenic lifestyle associated with several common skin disorders. Malassezia genomes encode myriad lipases and proteases thought to mediate lipid utilizati ... Full text Link to item Cite

Outbreak of Invasive Wound Mucormycosis in a Burn Unit Due to Multiple Strains of Mucor circinelloides f. circinelloides Resolved by Whole-Genome Sequencing.

Journal Article mBio · April 24, 2018 Mucorales are ubiquitous environmental molds responsible for mucormycosis in diabetic, immunocompromised, and severely burned patients. Small outbreaks of invasive wound mucormycosis (IWM) have already been reported in burn units without extensive microbio ... Full text Link to item Cite

Whole-Genome Analysis Illustrates Global Clonal Population Structure of the Ubiquitous Dermatophyte Pathogen Trichophyton rubrum.

Journal Article Genetics · April 2018 Dermatophytes include fungal species that infect humans, as well as those that also infect other animals or only grow in the environment. The dermatophyte species Trichophyton rubrum is a frequent cause of skin infection in immunocompetent individuals. Whi ... Full text Link to item Cite

RNAi is a critical determinant of centromere evolution in closely related fungi.

Journal Article Proc Natl Acad Sci U S A · March 20, 2018 The centromere DNA locus on a eukaryotic chromosome facilitates faithful chromosome segregation. Despite performing such a conserved function, centromere DNA sequence as well as the organization of sequence elements is rapidly evolving in all forms of euka ... Full text Link to item Cite

Had1 Is Required for Cell Wall Integrity and Fungal Virulence in Cryptococcus neoformans.

Journal Article G3 (Bethesda) · February 2, 2018 Calcineurin modulates environmental stress survival and virulence of the human fungal pathogen Cryptococcus neoformans Previously, we identified 44 putative calcineurin substrates, and proposed that the calcineurin pathway is branched to regulate targets i ... Full text Link to item Cite

Dissecting the Roles of the Calcineurin Pathway in Unisexual Reproduction, Stress Responses, and Virulence in Cryptococcus deneoformans.

Journal Article Genetics · February 2018 The Ca2+/calmodulin-dependent protein phosphatase calcineurin orchestrates sexual reproduction, stress responses, and virulence via branched downstream pathways in the opportunistic human fungal pathogen Cryptococcus neoformans The calcineurin-binding prot ... Full text Link to item Cite

PRM1 and KAR5 function in cell-cell fusion and karyogamy to drive distinct bisexual and unisexual cycles in the Cryptococcus pathogenic species complex.

Journal Article PLoS Genet · November 2017 Sexual reproduction is critical for successful evolution of eukaryotic organisms in adaptation to changing environments. In the opportunistic human fungal pathogens, the Cryptococcus pathogenic species complex, C. neoformans primarily undergoes bisexual re ... Full text Link to item Cite

FKBP12-Dependent Inhibition of Calcineurin Mediates Immunosuppressive Antifungal Drug Action in Malassezia.

Journal Article mBio · October 24, 2017 The genus Malassezia includes yeasts that are commonly found on the skin or hair of animals and humans as commensals and are associated with a number of skin disorders. We have previously developed an Agrobacterium tumefaciens transformation system effecti ... Full text Link to item Cite

Dynamics of parasitophorous vacuoles formed by the microsporidian pathogen Encephalitozoon cuniculi.

Journal Article Fungal Genet Biol · October 2017 It has been a long-standing debate if sexual development occurs in the microsporidian lineages. Previous studies, including morphological observations, ploidy analysis, and the presence of a sex-related locus, provided evidence of possible extant of sexual ... Full text Link to item Cite

Eukaryotic Sexual Reproduction Evoked "with a Little Help from My Friends".

Journal Article Cell · September 7, 2017 Bacteria and eukaryotes interact in many ways-from the microbiome that educates the mammalian immune system and enhances nutrition to relationships that are commensal, symbiotic, or parasitic. Now in an unexpected twist, King and colleagues have expanded t ... Full text Link to item Cite

Preface

Book · September 5, 2017 Cite

The fungal kingdom

Book · September 5, 2017 Fungi research and knowledge grew rapidly following recent advances in genetics and genomics. This book synthesizes new knowledge with existing information to stimulate new scientific questions and propel fungal scientists on to the next stages of research ... Full text Cite

Tracing Genetic Exchange and Biogeography of Cryptococcus neoformans var. grubii at the Global Population Level.

Journal Article Genetics · September 2017 Cryptococcus neoformans var. grubii is the causative agent of cryptococcal meningitis, a significant source of mortality in immunocompromised individuals, typically human immunodeficiency virus/AIDS patients from developing countries. Despite the worldwide ... Full text Link to item Cite

Natural mismatch repair mutations mediate phenotypic diversity and drug resistance in Cryptococcus deuterogattii.

Journal Article eLife · September 2017 Pathogenic microbes confront an evolutionary conflict between the pressure to maintain genome stability and the need to adapt to mounting external stresses. Bacteria often respond with elevated mutation rates, but little evidence exists of stable eukaryoti ... Full text Cite

Fungal genome and mating system transitions facilitated by chromosomal translocations involving intercentromeric recombination.

Journal Article PLoS Biol · August 2017 Species within the human pathogenic Cryptococcus species complex are major threats to public health, causing approximately 1 million annual infections globally. Cryptococcus amylolentus is the most closely known related species of the pathogenic Cryptococc ... Full text Link to item Cite

Construction of a Recyclable Genetic Marker and Serial Gene Deletions in the Human Pathogenic Mucorales Mucor circinelloides.

Journal Article G3 (Bethesda) · July 5, 2017 Mucor circinelloides is a human pathogen, biofuel producer, and model system that belongs to a basal fungal lineage; however, the genetics of this fungus are limited. In contrast to ascomycetes and basidiomycetes, basal fungal lineages have been understudi ... Full text Link to item Cite

Population genomics and the evolution of virulence in the fungal pathogen Cryptococcus neoformans.

Journal Article Genome Res · July 2017 Cryptococcus neoformans is an opportunistic fungal pathogen that causes approximately 625,000 deaths per year from nervous system infections. Here, we leveraged a unique, genetically diverse population of C. neoformans from sub-Saharan Africa, commonly iso ... Full text Link to item Cite

Elucidation of the calcineurin-Crz1 stress response transcriptional network in the human fungal pathogen Cryptococcus neoformans.

Journal Article PLoS Genet · April 2017 Calcineurin is a highly conserved Ca2+/calmodulin-dependent serine/threonine-specific protein phosphatase that orchestrates cellular Ca2+ signaling responses. In Cryptococcus neoformans, calcineurin is activated by multiple stresses including high temperat ... Full text Link to item Cite

Proteogenomics produces comprehensive and highly accurate protein-coding gene annotation in a complete genome assembly of Malassezia sympodialis.

Journal Article Nucleic Acids Res · March 17, 2017 Complete and accurate genome assembly and annotation is a crucial foundation for comparative and functional genomics. Despite this, few complete eukaryotic genomes are available, and genome annotation remains a major challenge. Here, we present a complete ... Full text Link to item Cite

A non-canonical RNA degradation pathway suppresses RNAi-dependent epimutations in the human fungal pathogen Mucor circinelloides.

Journal Article PLoS Genet · March 2017 Mucorales are a group of basal fungi that includes the casual agents of the human emerging disease mucormycosis. Recent studies revealed that these pathogens activate an RNAi-based pathway to rapidly generate drug-resistant epimutant strains when exposed t ... Full text Link to item Cite

Calcineurin in fungal virulence and drug resistance: Prospects for harnessing targeted inhibition of calcineurin for an antifungal therapeutic approach.

Journal Article Virulence · February 17, 2017 Increases in the incidence and mortality due to the major invasive fungal infections such as aspergillosis, candidiasis and cryptococcosis caused by the species of Aspergillus, Candida and Cryptococcus, are a growing threat to the immunosuppressed patient ... Full text Link to item Cite

New facets of antifungal therapy.

Journal Article Virulence · February 17, 2017 Invasive fungal infections remain a major cause of morbidity and mortality in immunocompromised patients, and such infections are a substantial burden to healthcare systems around the world. However, the clinically available armamentarium for invasive fung ... Full text Link to item Cite

Epidemiology and Evolution of Fungal Pathogens in Plants and Animals

Chapter · February 8, 2017 About 100,000 species of fungi have been described so far, of which a high percentage obtain nutrients by living in close association with other organisms, mainly plants. Many fungi are pathogenic and can have important impact on human health or lead to se ... Full text Cite

Sexual Reproduction in Dermatophytes.

Journal Article Mycopathologia · February 2017 Sexual reproduction is a rich source of genetic variation and commonly observed among fungi. Basically two different modes of sexual reproduction are observed in fungi, namely heterothallism where two compatible mating types are required to undergo mating ... Full text Link to item Cite

Rewiring of Signaling Networks Modulating Thermotolerance in the Human Pathogen Cryptococcus neoformans.

Journal Article Genetics · January 2017 Thermotolerance is a crucial virulence attribute for human pathogens, including the fungus Cryptococcus neoformans that causes fatal meningitis in humans. Loss of the protein kinase Sch9 increases C. neoformans thermotolerance, but its regulatory mechanism ... Full text Link to item Cite

Plants promote mating and dispersal of the human pathogenic fungus Cryptococcus.

Journal Article PLoS One · 2017 Infections due to Cryptococcus are a leading cause of fungal infections worldwide and are acquired as a result of environmental exposure to desiccated yeast or spores. The ability of Cryptococcus to grow, mate, and produce infectious propagules in associat ... Full text Link to item Cite

MTL genotypes, phenotypic switching, and susceptibility profiles of Candida parapsilosis species group compared to Lodderomyces elongisporus.

Journal Article PLoS One · 2017 Reference isolates of Candida parapsilosis (n = 8), Candida metapsilosis (n = 6), Candida orthopsilosis (n = 7), and Lodderomyces elongisporus (n = 11) were analyzed to gain insight into their pathobiology and virulence mechanisms. Initial evaluation using ... Full text Link to item Cite

Role of the Anillin Homologue in Cytokinesis of Cryptococcus neoformans.

Conference MOLECULAR BIOLOGY OF THE CELL · January 1, 2017 Link to item Cite

Gene Function Analysis in the Ubiquitous Human Commensal and Pathogen Malassezia Genus.

Journal Article mBio · November 29, 2016 UNLABELLED: The genus Malassezia includes 14 species that are found on the skin of humans and animals and are associated with a number of diseases. Recent genome sequencing projects have defined the gene content of all 14 species; however, to date, genetic ... Full text Link to item Cite

Dual action antifungal small molecule modulates multidrug efflux and TOR signaling.

Journal Article Nat Chem Biol · October 2016 There is an urgent need for new strategies to treat invasive fungal infections, which are a leading cause of human mortality. Here, we establish two activities of the natural product beauvericin, which potentiates the activity of the most widely deployed c ... Full text Link to item Cite

Metal Chelation as a Powerful Strategy to Probe Cellular Circuitry Governing Fungal Drug Resistance and Morphogenesis.

Journal Article PLoS Genet · October 2016 Fungal pathogens have evolved diverse strategies to sense host-relevant cues and coordinate cellular responses, which enable virulence and drug resistance. Defining circuitry controlling these traits opens new opportunities for chemical diversity in therap ... Full text Open Access Link to item Cite

Systematic functional analysis of kinases in the fungal pathogen Cryptococcus neoformans.

Journal Article Nat Commun · September 28, 2016 Cryptococcus neoformans is the leading cause of death by fungal meningoencephalitis; however, treatment options remain limited. Here we report the construction of 264 signature-tagged gene-deletion strains for 129 putative kinases, and examine their phenot ... Full text Open Access Link to item Cite

Calcineurin Targets Involved in Stress Survival and Fungal Virulence.

Journal Article PLoS Pathog · September 2016 Calcineurin governs stress survival, sexual differentiation, and virulence of the human fungal pathogen Cryptococcus neoformans. Calcineurin is activated by increased Ca2+ levels caused by stress, and transduces signals by dephosphorylating protein substra ... Full text Open Access Link to item Cite

Cancer-associated isocitrate dehydrogenase mutations induce mitochondrial DNA instability.

Journal Article Hum Mol Genet · August 15, 2016 A major advance in understanding the progression and prognostic outcome of certain cancers, such as low-grade gliomas, acute myeloid leukaemia, and chondrosarcomas, has been the identification of early-occurring mutations in the NADP+-dependent isocitrate ... Full text Link to item Cite

Expansion of Signal Transduction Pathways in Fungi by Extensive Genome Duplication.

Journal Article Curr Biol · June 20, 2016 Plants and fungi use light and other signals to regulate development, growth, and metabolism. The fruiting bodies of the fungus Phycomyces blakesleeanus are single cells that react to environmental cues, including light, but the mechanisms are largely unkn ... Full text Link to item Cite

Structures of Pathogenic Fungal FKBP12s Reveal Possible Self-Catalysis Function.

Journal Article mBio · April 26, 2016 UNLABELLED: Invasive fungal infections remain difficult to treat and require novel targeting strategies. The 12-kDa FK506-binding protein (FKBP12) is a ubiquitously expressed peptidyl-prolyl isomerase with considerable homology between fungal pathogens and ... Full text Link to item Cite

Gene Network Polymorphism Illuminates Loss and Retention of Novel RNAi Silencing Components in the Cryptococcus Pathogenic Species Complex.

Journal Article PLoS Genet · March 2016 RNAi is a ubiquitous pathway that serves central functions throughout eukaryotes, including maintenance of genome stability and repression of transposon expression and movement. However, a number of organisms have lost their RNAi pathways, including the mo ... Full text Open Access Link to item Cite

From Two to One: Unipolar Sexual Reproduction.

Journal Article Fungal Biol Rev · December 1, 2015 While sexual reproduction is universal in eukaryotes, and shares conserved core features, the specific aspects of sexual reproduction can differ dramatically from species to species. This is also true in Fungi. Among fungal species, mating determination ca ... Full text Link to item Cite

Evolution of sexual reproduction: a view from the Fungal Kingdom supports an evolutionary epoch with sex before sexes.

Journal Article Fungal Biol Rev · December 1, 2015 Sexual reproduction is conserved throughout each supergroup within the eukaryotic tree of life, and therefore thought to have evolved once and to have been present in the last eukaryotic common ancestor (LECA). Given the antiquity of sex, there are feature ... Full text Link to item Cite

An Antifungal Combination Matrix Identifies a Rich Pool of Adjuvant Molecules that Enhance Drug Activity against Diverse Fungal Pathogens.

Journal Article Cell Rep · November 17, 2015 There is an urgent need to identify new treatments for fungal infections. By combining sub-lethal concentrations of the known antifungals fluconazole, caspofungin, amphotericin B, terbinafine, benomyl, and cyprodinil with ∼3,600 compounds in diverse fungal ... Full text Link to item Cite

Genus-Wide Comparative Genomics of Malassezia Delineates Its Phylogeny, Physiology, and Niche Adaptation on Human Skin.

Journal Article PLoS Genet · November 2015 Malassezia is a unique lipophilic genus in class Malasseziomycetes in Ustilaginomycotina, (Basidiomycota, fungi) that otherwise consists almost exclusively of plant pathogens. Malassezia are typically isolated from warm-blooded animals, are dominant member ... Full text Link to item Cite

Calcineurin orchestrates dimorphic transitions, antifungal drug responses and host-pathogen interactions of the pathogenic mucoralean fungus Mucor circinelloides.

Journal Article Mol Microbiol · September 2015 Calcineurin plays essential roles in virulence and growth of pathogenic fungi and is a target of the natural products FK506 and Cyclosporine A. In the pathogenic mucoralean fungus Mucor circinelloides, calcineurin mutation or inhibition confers a yeast-loc ... Full text Link to item Cite

Genome Evolution and Innovation across the Four Major Lineages of Cryptococcus gattii.

Journal Article mBio · September 1, 2015 UNLABELLED: Cryptococcus gattii is a fungal pathogen of humans, causing pulmonary infections in otherwise healthy hosts. To characterize genomic variation among the four major lineages of C. gattii (VGI, -II, -III, and -IV), we generated, annotated, and co ... Full text Link to item Cite

Genomics and Transcriptomics Analyses of the Oil-Accumulating Basidiomycete Yeast Trichosporon oleaginosus: Insights into Substrate Utilization and Alternative Evolutionary Trajectories of Fungal Mating Systems.

Journal Article mBio · July 21, 2015 UNLABELLED: Microbial fermentation of agro-industrial waste holds great potential for reducing the environmental impact associated with the production of lipids for industrial purposes from plant biomass. However, the chemical complexity of many residues c ... Full text Link to item Cite

Cryptococcosis Serotypes Impact Outcome and Provide Evidence of Cryptococcus neoformans Speciation.

Journal Article mBio · June 9, 2015 UNLABELLED: Cryptococcus neoformans is a human opportunistic fungal pathogen causing severe disseminated meningoencephalitis, mostly in patients with cellular immune defects. This species is divided into three serotypes: A, D, and the AD hybrid. Our object ... Full text Link to item Cite

Cryptococcal osteomyelitis in an adolescent survivor of T-cell acute lymphoblastic leukemia.

Journal Article Pediatr Infect Dis J · June 2015 Cryptococcosis is infrequent in children, and isolated cryptococcal osteomyelitis is rarely encountered. Here, we describe a 14-year-old patient in remission from T-cell acute lymphoblastic leukemia with osteomyelitis because of Cryptococcus neoformans var ... Full text Link to item Cite

Unisexual versus bisexual mating in Cryptococcus neoformans: Consequences and biological impacts.

Journal Article Fungal Genet Biol · May 2015 Cryptococcus neoformans is an opportunistic human fungal pathogen and can undergo both bisexual and unisexual mating. Despite the fact that one mating type is dispensable for unisexual mating, the two sexual cycles share surprisingly similar features. Both ... Full text Link to item Cite

Systematic functional profiling of transcription factor networks in Cryptococcus neoformans.

Journal Article Nat Commun · April 7, 2015 Cryptococcus neoformans causes life-threatening meningoencephalitis in humans, but its overall biological and pathogenic regulatory circuits remain elusive, particularly due to the presence of an evolutionarily divergent set of transcription factors (TFs). ... Full text Link to item Cite

A case of cryptococcus gattii in Western Florida: An aggressive pathogen in an immunocompetent host

Journal Article Infectious Diseases in Clinical Practice · March 12, 2015 Background Cryptococcus gattii is an environmental pathogenic yeast that produces disease in the skin, the respiratory tract, and the central nervous system of both immunocompromised and immunocompetent hosts. The incidence of C. gattii disease is increasi ... Full text Cite

Network-assisted genetic dissection of pathogenicity and drug resistance in the opportunistic human pathogenic fungus Cryptococcus neoformans.

Journal Article Sci Rep · March 5, 2015 Cryptococcus neoformans is an opportunistic human pathogenic fungus that causes meningoencephalitis. Due to the increasing global risk of cryptococcosis and the emergence of drug-resistant strains, the development of predictive genetics platforms for the r ... Full text Link to item Cite

Sex in the Mucoralean fungi.

Journal Article Mycoses · December 2014 Sexual development is extant in virtually all eukaryotic species, including throughout the kingdom Fungi. Positioned within the opisthokonts along with metazoans, fungi serve as model systems to elucidate the genetics and impact of sexual development. Basa ... Full text Link to item Cite

Distinct and redundant roles of exonucleases in Cryptococcus neoformans: implications for virulence and mating.

Journal Article Fungal Genet Biol · December 2014 Opportunistic pathogens like Cryptococcus neoformans are constantly exposed to changing environments, in their natural habitat as well as when encountering a human host. This requires a coordinated program to regulate gene expression that can act at the le ... Full text Link to item Cite

Unisexual reproduction drives meiotic recombination and phenotypic and karyotypic plasticity in Cryptococcus neoformans.

Journal Article PLoS Genet · December 2014 In fungi, unisexual reproduction, where sexual development is initiated without the presence of two compatible mating type alleles, has been observed in several species that can also undergo traditional bisexual reproduction, including the important human ... Full text Link to item Cite

Unisexual reproduction reverses Muller's ratchet.

Journal Article Genetics · November 2014 Cryptococcus neoformans is a pathogenic basidiomycetous fungus that engages in outcrossing, inbreeding, and selfing forms of unisexual reproduction as well as canonical sexual reproduction between opposite mating types. Long thought to be clonal, >99% of s ... Full text Link to item Cite

Sex and the Microsporidia

Chapter · October 20, 2014 In this chapter, the author brings the various types of evidence for sexuality and asexuality in the microsporidia, ranging from observations of life cycles under the light and electron microscope to population genetic analyses of recombination and surveys ... Full text Cite

Antifungal drug resistance evoked via RNAi-dependent epimutations.

Journal Article Nature · September 25, 2014 Microorganisms evolve via a range of mechanisms that may include or involve sexual/parasexual reproduction, mutators, aneuploidy, Hsp90 and even prions. Mechanisms that may seem detrimental can be repurposed to generate diversity. Here we show that the hum ... Full text Link to item Cite

Cryptococcus gattii VGIII Isolates Causing Infections in HIV/AIDS Patients in Southern California: Identification of the Local Environmental Source as Arboreal

Journal Article PLoS Pathogens · August 21, 2014 Ongoing Cryptococcus gattii outbreaks in the Western United States and Canada illustrate the impact of environmental reservoirs and both clonal and recombining propagation in driving emergence and expansion of microbial pathogens. C. gattii comprises four ... Full text Open Access Cite

Cryptococcus gattii VGIII isolates causing infections in HIV/AIDS patients in Southern California: identification of the local environmental source as arboreal.

Journal Article PLoS Pathog · August 2014 Ongoing Cryptococcus gattii outbreaks in the Western United States and Canada illustrate the impact of environmental reservoirs and both clonal and recombining propagation in driving emergence and expansion of microbial pathogens. C. gattii comprises four ... Full text Link to item Cite

Sexual reproduction of human fungal pathogens.

Journal Article Cold Spring Harb Perspect Med · August 1, 2014 We review here recent advances in our understanding of sexual reproduction in fungal pathogens that commonly infect humans, including Candida albicans, Cryptococcus neoformans/gattii, and Aspergillus fumigatus. Where appropriate or relevant, we introduce f ... Full text Link to item Cite

Highly recombinant VGII Cryptococcus gattii population develops clonal outbreak clusters through both sexual macroevolution and asexual microevolution.

Journal Article mBio · July 29, 2014 An outbreak of the fungal pathogen Cryptococcus gattii began in the Pacific Northwest (PNW) in the late 1990s. This outbreak consists of three clonal subpopulations: VGIIa/major, VGIIb/minor, and VGIIc/novel. Both VGIIa and VGIIc are unique to the PNW and ... Full text Link to item Cite

Analysis of a food-borne fungal pathogen outbreak: virulence and genome of a Mucor circinelloides isolate from yogurt.

Journal Article mBio · July 8, 2014 Food-borne pathogens are ongoing problems, and new pathogens are emerging. The impact of fungi, however, is largely underestimated. Recently, commercial yogurts contaminated with Mucor circinelloides were sold, and >200 consumers became ill with nausea, vo ... Full text Link to item Cite

Calcineurin controls hyphal growth, virulence, and drug tolerance of Candida tropicalis.

Journal Article Eukaryot Cell · July 2014 Candida tropicalis, a species closely related to Candida albicans, is an emerging fungal pathogen associated with high mortality rates of 40 to 70%. Like C. albicans and Candida dubliniensis, C. tropicalis is able to form germ tubes, pseudohyphae, and hyph ... Full text Link to item Cite

Analysis of the genome and transcriptome of Cryptococcus neoformans var. grubii reveals complex RNA expression and microevolution leading to virulence attenuation.

Journal Article PLoS Genet · April 2014 Cryptococcus neoformans is a pathogenic basidiomycetous yeast responsible for more than 600,000 deaths each year. It occurs as two serotypes (A and D) representing two varieties (i.e. grubii and neoformans, respectively). Here, we sequenced the genome and ... Full text Open Access Link to item Cite

Endolysosomal membrane trafficking complexes drive nutrient-dependent TORC1 signaling to control cell growth in Saccharomyces cerevisiae.

Journal Article Genetics · April 2014 The rapamycin-sensitive and endomembrane-associated TORC1 pathway controls cell growth in response to nutrients in eukaryotes. Mutations in class C Vps (Vps-C) complexes are synthetically lethal with tor1 mutations and confer rapamycin hypersensitivity in ... Full text Link to item Cite

Origins of eukaryotic sexual reproduction.

Journal Article Cold Spring Harb Perspect Biol · March 1, 2014 Sexual reproduction is a nearly universal feature of eukaryotic organisms. Given its ubiquity and shared core features, sex is thought to have arisen once in the last common ancestor to all eukaryotes. Using the perspectives of molecular genetics and cell ... Full text Link to item Cite

Estrogen receptor antagonists are anti-cryptococcal agents that directly bind EF hand proteins and synergize with fluconazole in vivo.

Journal Article mBio · February 11, 2014 UNLABELLED: Cryptococcosis is an infectious disease of global significance for which new therapies are needed. Repurposing previously developed drugs for new indications can expedite the translation of new therapies from bench to beside. Here, we character ... Full text Link to item Cite

Unseen sex in ancient virgin fungi.

Journal Article New Phytol · January 2014 Full text Link to item Cite

Unisexual reproduction.

Journal Article Adv Genet · 2014 Sexual reproduction is ubiquitous throughout the eukaryotic kingdom, but the capacity of pathogenic fungi to undergo sexual reproduction has been a matter of intense debate. Pathogenic fungi maintained a complement of conserved meiotic genes but the popula ... Full text Link to item Cite

Cryptococcus neoformans hyperfilamentous strain is hypervirulent in a murine model of cryptococcal meningoencephalitis.

Journal Article PLoS One · 2014 Cryptococcus neoformans is a human fungal pathogen that causes lethal infections of the lung and central nervous system in immunocompromised individuals. C. neoformans has a defined bipolar sexual life cycle with a and α mating types. During the sexual cyc ... Full text Link to item Cite

Phylogenetic analysis of phenotypically characterized Cryptococcus laurentii isolates reveals high frequency of cryptic species.

Journal Article PLoS One · 2014 BACKGROUND: Although Cryptococcus laurentii has been considered saprophytic and its taxonomy is still being described, several cases of human infections have already reported. This study aimed to evaluate molecular aspects of C. laurentii isolates from Bra ... Full text Link to item Cite

Unisexual reproduction of Cryptococcus gattii.

Journal Article PLoS One · 2014 Cryptococcus gattii is a basidiomycetous human fungal pathogen that typically causes infection in tropical and subtropical regions and is responsible for an ongoing outbreak in immunocompetent individuals on Vancouver Island and in the Pacific Northwest of ... Full text Link to item Cite

RNAi function, diversity, and loss in the fungal kingdom.

Journal Article Chromosome Res · December 2013 RNAi is conserved and has been studied in a broad cross-section of the fungal kingdom, including Neurospora crassa, Schizosaccharomyces pombe, Cryptococcus neoformans, and Mucor circinelloides. And yet well known species, including the model yeast Saccharo ... Full text Link to item Cite

Evolution of sex: mating rituals of a pre-metazoan.

Journal Article Curr Biol · November 18, 2013 Sex is pervasive throughout eukaryotes, yet many species have not been caught in the act. Now, a sexual cycle has been discovered in the choanoflagellate Salpingoeca rosetta, a pre-metazoan evolutionary model, opening a window on metazoan sexual evolution. ... Full text Link to item Cite

Evolution of Virulence in Eukaryotic Microbes

Book · October 28, 2013 A unique and timely review of the emergence of eukaryotic virulence in fungi, oomycetes, and protozoa, as they affect both animals and plants Evolution of Virulence in Eukaryotic Microbes addresses new developments in defining the molecular basis of virule ... Full text Cite

Ordered kinetochore assembly in the human-pathogenic basidiomycetous yeast Cryptococcus neoformans.

Journal Article mBio · October 1, 2013 UNLABELLED: Kinetochores facilitate interaction between chromosomes and the spindle apparatus. The formation of a metazoan trilayered kinetochore is an ordered event in which inner, middle, and outer layers assemble during disassembly of the nuclear envelo ... Full text Link to item Cite

Synthesis and antifungal activities of miltefosine analogs.

Journal Article Bioorg Med Chem Lett · September 1, 2013 Miltefosine is an alkylphosphocholine that shows broad-spectrum in vitro antifungal activities and limited in vivo efficacy in mouse models of cryptococcosis. To further explore the potential of this class of compounds for the treatment of systemic mycoses ... Full text Link to item Cite

Unisexual and heterosexual meiotic reproduction generate aneuploidy and phenotypic diversity de novo in the yeast Cryptococcus neoformans.

Journal Article PLoS Biol · September 2013 Aneuploidy is known to be deleterious and underlies several common human diseases, including cancer and genetic disorders such as trisomy 21 in Down's syndrome. In contrast, aneuploidy can also be advantageous and in fungi confers antifungal drug resistanc ... Full text Link to item Cite

Unisexual reproduction enhances fungal competitiveness by promoting habitat exploration via hyphal growth and sporulation.

Journal Article Eukaryot Cell · August 2013 Unisexual reproduction is a novel homothallic sexual cycle recently discovered in both ascomycetous and basidiomycetous pathogenic fungi. It is a form of selfing that induces the yeast-to-hyphal dimorphic transition in isolates of the α mating type of the ... Full text Link to item Cite

Molecular and genetic evidence for a tetrapolar mating system in the basidiomycetous yeast Kwoniella mangrovensis and two novel sibling species.

Journal Article Eukaryot Cell · May 2013 Kwoniella mangrovensis has been described as a sexual species with a bipolar mating system. Phylogenetic analysis of multiple genes places this species together with Kwoniella heveanensis in the Kwoniella clade, a sister clade to that containing two pathog ... Full text Link to item Cite

Sex-induced silencing operates during opposite-sex and unisexual reproduction in Cryptococcus neoformans.

Journal Article Genetics · April 2013 Cryptococcus neoformans is a human fungal pathogen that undergoes a dimorphic transition from yeast to hyphae during a-α opposite-sex mating and α-α unisexual reproduction (same-sex mating). Infectious spores are generated during both processes. We previou ... Full text Link to item Cite

Cryptococcus neoformans copper detoxification machinery is critical for fungal virulence.

Journal Article Cell Host Microbe · March 13, 2013 Copper (Cu) is an essential metal that is toxic at high concentrations. Thus, pathogens often rely on host Cu for growth, but host cells can hyperaccumulate Cu to exert antimicrobial effects. The human fungal pathogen Cryptococcus neoformans encodes many C ... Full text Link to item Cite

Calcineurin governs thermotolerance and virulence of Cryptococcus gattii.

Journal Article G3 (Bethesda) · March 2013 The pathogenic yeast Cryptococcus gattii, which is causing an outbreak in the Pacific Northwest region of North America, causes life-threatening pulmonary infections and meningoencephalitis in healthy individuals, unlike Cryptococcus neoformans, which comm ... Full text Link to item Cite

Genomic insights into the atopic eczema-associated skin commensal yeast Malassezia sympodialis.

Journal Article mBio · January 22, 2013 UNLABELLED: Malassezia commensal yeasts are associated with a number of skin disorders, such as atopic eczema/dermatitis and dandruff, and they also can cause systemic infections. Here we describe the 7.67-Mbp genome of Malassezia sympodialis, a species as ... Full text Link to item Cite

Polyporales genomes reveal the genetic architecture underlying tetrapolar and bipolar mating systems.

Journal Article Mycologia · 2013 The process of mating in Basidiomycota is regulated by homeodomain-encoding genes (HD) and pheromones and G protein-coupled pheromone receptor genes (P/R). Whether these genes are actually involved in determining mating type distinguishes mating systems th ... Full text Link to item Cite

Identification of the mating-type (MAT) locus that controls sexual reproduction of Blastomyces dermatitidis.

Journal Article Eukaryot Cell · January 2013 Blastomyces dermatitidis is a dimorphic fungal pathogen that primarily causes blastomycosis in the midwestern and northern United States and Canada. While the genes controlling sexual development have been known for a long time, the genes controlling sexua ... Full text Link to item Cite

Posaconazole exhibits in vitro and in vivo synergistic antifungal activity with caspofungin or FK506 against Candida albicans.

Journal Article PLoS One · 2013 The object of this study was to test whether posaconazole, a broad-spectrum antifungal agent inhibiting ergosterol biosynthesis, exhibits synergy with the β-1,3 glucan synthase inhibitor caspofungin or the calcineurin inhibitor FK506 against the human fung ... Full text Link to item Cite

Evolution of fungal sexual reproduction.

Journal Article Mycologia · 2013 We review here recent advances in our understanding of the genetic, molecular and genomic basis of sex determination and sexual reproduction in the fungal kingdom as a window on the evolution of sex in eukaryotes more generally. In particular, we focus on ... Full text Link to item Cite

Reconstructing genome evolution in historic samples of the Irish potato famine pathogen.

Journal Article Nat Commun · 2013 Responsible for the Irish potato famine of 1845-49, the oomycete pathogen Phytophthora infestans caused persistent, devastating outbreaks of potato late blight across Europe in the 19th century. Despite continued interest in the history and spread of the p ... Full text Link to item Cite

Development of an aerosol model of Cryptococcus reveals humidity as an important factor affecting the viability of Cryptococcus during aerosolization.

Journal Article PLoS One · 2013 Cryptococcus is an emerging global health threat that is annually responsible for over 1,000,000 infections and one third of all AIDS patient deaths. There is an ongoing outbreak of cryptococcosis in the western United States and Canada. Cryptococcosis is ... Full text Link to item Cite

Genomic insights into the atopic eczema-associated skin commensal yeast Malassezia sympodialis.

Journal Article mBio · 2013 ABSTRACT: Malassezia commensal yeasts are associated with a number of skin disorders, such as atopic eczema/dermatitis and dandruff, and they also can cause systemic infections. Here we describe the 7.67-Mbp genome of Malassezia sympodialis, a species asso ... Full text Cite

Transmission of Hypervirulence traits via sexual reproduction within and between lineages of the human fungal pathogen cryptococcus gattii.

Journal Article PLoS Genet · 2013 Since 1999 a lineage of the pathogen Cryptococcus gattii has been infecting humans and other animals in Canada and the Pacific Northwest of the USA. It is now the largest outbreak of a life-threatening fungal infection in a healthy population in recorded h ... Full text Link to item Cite

Calcineurin plays key roles in the dimorphic transition and virulence of the human pathogenic zygomycete Mucor circinelloides.

Journal Article PLoS Pathog · 2013 Many pathogenic fungi are dimorphic and switch between yeast and filamentous states. This switch alters host-microbe interactions and is critical for pathogenicity. However, in zygomycetes, whether dimorphism contributes to virulence is a central unanswere ... Full text Link to item Cite

Genetic circuits that govern bisexual and unisexual reproduction in Cryptococcus neoformans.

Journal Article PLoS Genet · 2013 Cryptococcus neoformans is a human fungal pathogen with a defined sexual cycle. Nutrient-limiting conditions and pheromones induce a dimorphic transition from unicellular yeast to multicellular hyphae and the production of infectious spores. Sexual reprodu ... Full text Link to item Cite

Cryptococcus gattii, no longer an accidental pathogen?

Journal Article Curr Fungal Infect Rep · December 2012 Cryptococcus gattii is an environmentally occurring pathogen that is responsible for causing cryptococcosis marked by pneumonia and meningoencephalitis in humans and animals. C. gattii can form long-term associations with trees and soil resulting in the pr ... Full text Link to item Cite

Pleiotropic roles of the Msi1-like protein Msl1 in Cryptococcus neoformans.

Journal Article Eukaryot Cell · December 2012 Msi1-like (MSIL) proteins contain WD40 motifs and have a pleiotropic cellular function as negative regulators of the Ras/cyclic AMP (cAMP) pathway and components of chromatin assembly factor 1 (CAF-1), yet they have not been studied in fungal pathogens. He ... Full text Link to item Cite

Comparative genome analysis of Trichophyton rubrum and related dermatophytes reveals candidate genes involved in infection.

Journal Article mBio · December 1, 2012 The major cause of athlete's foot is Trichophyton rubrum, a dermatophyte or fungal pathogen of human skin. To facilitate molecular analyses of the dermatophytes, we sequenced T. rubrum and four related species, Trichophyton tonsurans, Trichophyton equinum, ... Cite

Should Y stay or should Y go: the evolution of non-recombining sex chromosomes.

Journal Article Bioessays · November 2012 Gradual degradation seems inevitable for non-recombining sex chromosomes. This has been supported by the observation of degenerated non-recombining sex chromosomes in a variety of species. The human Y chromosome has also degenerated significantly during it ... Full text Link to item Cite

Pseudohyphal growth of Cryptococcus neoformans is a reversible dimorphic transition in response to ammonium that requires Amt1 and Amt2 ammonium permeases.

Journal Article Eukaryot Cell · November 2012 Cryptococcus neoformans is a human-pathogenic basidiomycete that commonly infects HIV/AIDS patients to cause meningoencephalitis (7, 19). C. neoformans grows as a budding yeast during vegetative growth or as hyphae during sexual reproduction. Pseudohyphal ... Full text Link to item Cite

Surfactant protein D facilitates Cryptococcus neoformans infection.

Journal Article Infect Immun · July 2012 Concurrent with the global escalation of the AIDS pandemic, cryptococcal infections are increasing and are of significant medical importance. Furthermore, Cryptococcus neoformans has become a primary human pathogen, causing infection in seemingly healthy i ... Full text Link to item Cite

Gene conversion occurs within the mating-type locus of Cryptococcus neoformans during sexual reproduction.

Journal Article PLoS Genet · July 2012 Meiotic recombination of sex chromosomes is thought to be repressed in organisms with heterogametic sex determination (e.g. mammalian X/Y chromosomes), due to extensive divergence and chromosomal rearrangements between the two chromosomes. However, proper ... Full text Link to item Cite

The Paleozoic origin of enzymatic lignin decomposition reconstructed from 31 fungal genomes.

Journal Article Science · June 29, 2012 Wood is a major pool of organic carbon that is highly resistant to decay, owing largely to the presence of lignin. The only organisms capable of substantial lignin decay are white rot fungi in the Agaricomycetes, which also contains non-lignin-degrading br ... Full text Link to item Cite

Know your enemy: how to build and vanquish a global fungal scourge.

Journal Article Mycopathologia · June 2012 The 8th International Conference on Cryptococcus and Cryptococcosis, chaired by Maurizio Del Poeta (Medical University of South Carolina), and organized together with June Kwon-Chung (National Institute of Allergy and Infectious Diseases), Stuart Levitz (U ... Full text Link to item Cite

Function of Cryptococcus neoformans KAR7 (SEC66) in karyogamy during unisexual and opposite-sex mating.

Journal Article Eukaryot Cell · June 2012 The human basidiomycetous fungal pathogen Cryptococcus neoformans serves as a model fungus to study sexual development and produces infectious propagules, basidiospores, via the sexual cycle. Karyogamy is the process of nuclear fusion and an essential step ... Full text Link to item Cite

Convergent Evolution of Calcineurin Pathway Roles in Thermotolerance and Virulence in Candida glabrata.

Journal Article G3 (Bethesda) · June 2012 Candida glabrata is an emerging human fungal pathogen that is frequently drug tolerant, resulting in difficulties in treatment and a higher mortality in immunocompromised patients. The calcium-activated protein phosphatase calcineurin plays critical roles ... Full text Link to item Cite

Rapamycin exerts antifungal activity in vitro and in vivo against Mucor circinelloides via FKBP12-dependent inhibition of Tor.

Journal Article Eukaryot Cell · March 2012 The zygomycete Mucor circinelloides is an opportunistic fungal pathogen that commonly infects patients with malignancies, diabetes mellitus, and solid organ transplants. Despite the widespread use of antifungal therapy in the management of zygomycosis, the ... Full text Link to item Cite

Comparative analysis of calcineurin signaling between Candida dubliniensis and Candida albicans

Journal Article Communicative and Integrative Biology · March 1, 2012 Candida dubliniensis, an emerging fungal pathogen, is the closest known species to the established pathogenic species Candida albicans. Despite the fact that these two species share.80% genome sequence identity, they exhibit distinct properties such as les ... Full text Cite

Discovery of a modified tetrapolar sexual cycle in Cryptococcus amylolentus and the evolution of MAT in the Cryptococcus species complex.

Journal Article PLoS Genet · 2012 Sexual reproduction in fungi is governed by a specialized genomic region called the mating-type locus (MAT). The human fungal pathogenic and basidiomycetous yeast Cryptococcus neoformans has evolved a bipolar mating system (a, α) in which the MAT locus is ... Full text Link to item Cite

Calcineurin is required for pseudohyphal growth, virulence, and drug resistance in Candida lusitaniae.

Journal Article PLoS One · 2012 Candida lusitaniae is an emerging fungal pathogen that infects immunocompromised patients including HIV/AIDS, cancer, and neonatal pediatric patients. Though less prevalent than other Candida species, C. lusitaniae is unique in its ability to develop resis ... Full text Link to item Cite

Calcofluor white combination antifungal treatments for Trichophyton rubrum and Candida albicans.

Journal Article PLoS One · 2012 Superficial mycoses caused by dermatophyte fungi are among the most common infections worldwide, yet treatment is restricted by limited effective drugs available, drug toxicity, and emergence of drug resistance. The stilbene fluorescent brightener calcoflu ... Full text Link to item Cite

Transgene induced co-suppression during vegetative growth in Cryptococcus neoformans.

Journal Article PLoS Genet · 2012 Introduction of DNA sequences into the genome often results in homology-dependent gene silencing in organisms as diverse as plants, fungi, flies, nematodes, and mammals. We previously showed in Cryptococcus neoformans that a repeat transgene array can indu ... Full text Link to item Cite

Global analysis of the evolution and mechanism of echinocandin resistance in Candida glabrata.

Journal Article PLoS Pathog · 2012 The evolution of drug resistance has a profound impact on human health. Candida glabrata is a leading human fungal pathogen that can rapidly evolve resistance to echinocandins, which target cell wall biosynthesis and are front-line therapeutics for Candida ... Full text Link to item Cite

A unique chromosomal rearrangement in the Cryptococcus neoformans var. grubii type strain enhances key phenotypes associated with virulence.

Journal Article mBio · 2012 UNLABELLED: The accumulation of genomic structural variation between closely related populations over time can lead to reproductive isolation and speciation. The fungal pathogen Cryptococcus is thought to have recently diversified, forming a species comple ... Full text Link to item Cite

A flucytosine-responsive Mbp1/Swi4-like protein, Mbs1, plays pleiotropic roles in antifungal drug resistance, stress response, and virulence of Cryptococcus neoformans.

Journal Article Eukaryot Cell · January 2012 Cryptococcosis, caused by the basidiomycetous fungus Cryptococcus neoformans, is responsible for more than 600,000 deaths annually in AIDS patients. Flucytosine is one of the most commonly used antifungal drugs for its treatment, but its resistance and reg ... Full text Link to item Cite

Profiling a killer, the development of Cryptococcus neoformans.

Journal Article FEMS Microbiol Rev · January 2012 The ability of fungi to transition between unicellular and multicellular growth has a profound impact on our health and the economy. Many important fungal pathogens of humans, animals, and plants are dimorphic, and the ability to switch between morphologic ... Full text Link to item Cite

Comparative genome analysis of Trichophyton rubrum and related dermatophytes reveals candidate genes involved in infection.

Journal Article mBio · 2012 The major cause of athlete's foot is Trichophyton rubrum, a dermatophyte or fungal pathogen of human skin. To facilitate molecular analyses of the dermatophytes, we sequenced T. rubrum and four related species, Trichophyton tonsurans, Trichophyton equinum, ... Full text Link to item Cite

Genetic Diversity and Genomic Plasticity of Cryptococcus neoformans AD Hybrid Strains.

Journal Article G3 (Bethesda) · January 2012 Natural hybridization between two strains, varieties, or species is a common phenomenon in both plants and animals. Although hybridization may skew established gene pools, it generates population diversity efficiently and sometimes results in the emergence ... Full text Link to item Cite

The C2 domain protein Cts1 functions in the calcineurin signaling circuit during high-temperature stress responses in Cryptococcus neoformans.

Journal Article Eukaryot Cell · December 2011 Calcineurin is a conserved calcium/calmodulin-dependent serine/threonine-specific protein phosphatase that acts in cell stress responses. Calcineurin is essential for growth at 37°C and for virulence of the human fungal pathogen Cryptococcus neoformans, bu ... Full text Link to item Cite

Cryptococcus gattii genotype VGI infection in New England.

Journal Article Pediatr Infect Dis J · December 2011 Cryptococcus gattii is a known, emerging infectious disease pathogen predominantly in the Pacific Northwest, the United States, and British Columbia, Canada. We report a case of an immunocompetent adolescent from New England who had severe pulmonary and ce ... Full text Link to item Cite

Epidemiology and evolution of fungal pathogens in plants and animals

Journal Article · December 1, 2011 This chapter discusses the main pathogenic fungi parasitizing humans, animals, and plants, and having important consequences on human health or human activities. It discusses the modern molecular tools used for epidemiology and population genetics of funga ... Full text Cite

Calcineurin colocalizes with P-bodies and stress granules during thermal stress in Cryptococcus neoformans.

Journal Article Eukaryot Cell · November 2011 Calcineurin is a calcium-calmodulin-activated serine/threonine-specific phosphatase that operates during cellular responses to stress and plays a prominent role in transcriptional control, whereas regulatory events beyond transcription are less well charac ... Full text Link to item Cite

Deletion of Cryptococcus neoformans AIF ortholog promotes chromosome aneuploidy and fluconazole-resistance in a metacaspase-independent manner.

Journal Article PLoS Pathog · November 2011 Apoptosis is a form of programmed cell death critical for development and homeostasis in multicellular organisms. Apoptosis-like cell death (ALCD) has been described in several fungi, including the opportunistic human pathogen Cryptococcus neoformans. In a ... Full text Link to item Cite

Cryptococcus gattii: an emerging fungal pathogen infecting humans and animals.

Journal Article Microbes Infect · October 2011 Infectious fungi are among a broad group of microbial pathogens that has and continues to emerge concomitantly due to the global AIDS pandemic as well as an overall increase of patients with compromised immune systems. In addition, many pathogens have been ... Full text Link to item Cite

A diverse population of Cryptococcus gattii molecular type VGIII in southern Californian HIV/AIDS patients.

Journal Article PLoS Pathog · September 2011 Cryptococcus gattii infections in southern California have been reported in patients with HIV/AIDS. In this study, we examined the molecular epidemiology, population structure, and virulence attributes of isolates collected from HIV/AIDS patients in Los An ... Full text Link to item Cite

Is sex necessary?

Journal Article BMC Biol · August 31, 2011 Fungal sexual reproductive modes have markedly high diversity and plasticity, and asexual species have been hypothesized to arise frequently from sexual fungal species. A recent study on the red yeasts provides further support for the notion that sexual an ... Full text Link to item Cite

Unique evolution of the UPR pathway with a novel bZIP transcription factor, Hxl1, for controlling pathogenicity of Cryptococcus neoformans.

Journal Article PLoS Pathog · August 2011 In eukaryotic cells, the unfolded protein response (UPR) pathway plays a crucial role in cellular homeostasis of the endoplasmic reticulum (ER) during exposure to diverse environmental conditions that cause ER stress. Here we report that the human fungal p ... Full text Link to item Cite

Calcineurin controls drug tolerance, hyphal growth, and virulence in Candida dubliniensis.

Journal Article Eukaryot Cell · June 2011 Candida dubliniensis is an emerging pathogenic yeast species closely related to Candida albicans and frequently found colonizing or infecting the oral cavities of HIV/AIDS patients. Drug resistance during C. dubliniensis infection is common and constitutes ... Full text Link to item Cite

Sporangiospore size dimorphism is linked to virulence of Mucor circinelloides.

Journal Article PLoS Pathog · June 2011 Mucor circinelloides is a zygomycete fungus and an emerging opportunistic pathogen in immunocompromised patients, especially transplant recipients and in some cases otherwise healthy individuals. We have discovered a novel example of size dimorphism linked ... Full text Link to item Cite

Microbial Pathogens in the Fungal Kingdom.

Journal Article Fungal Biol Rev · March 1, 2011 The fungal kingdom is vast, spanning ~1.5 to as many as 5 million species diverse as unicellular yeasts, filamentous fungi, mushrooms, lichens, and both plant and animal pathogens. The fungi are closely aligned with animals in one of the six to eight super ... Full text Link to item Cite

Tourism implications of cryptococcus gattii in the southeastern USA

Chapter · January 1, 2011 In 2007, the first confirmed case of Cryptococcus gattii was reported in the state of North Carolina, USA. An otherwise healthy human immunodeficiency virus (HIV) negative male patient presented with a large upper thigh cryptococcoma in February, which was ... Cite

Association of calcineurin with the COPI protein Sec28 and the COPII protein Sec13 revealed by quantitative proteomics.

Journal Article PLoS One · 2011 Calcineurin is a calcium-calmodulin-dependent serine/threonine specific protein phosphatase operating in key cellular processes governing responses to extracellular cues. Calcineurin is essential for growth at high temperature and virulence of the human fu ... Full text Link to item Cite

Validation of kwoniella heveanensis, teleomorph of the basidiomycetous yeast Cryptococcus heveanensis

Journal Article Mycotaxon · January 1, 2011 Kwoniella heveanensis, recently published in an electronic journal and without a designated holotype, is validated as the name of the newly discovered teleomorph of Cryptococcus heveanensis. © 2011. Mycotaxon, Ltd. ... Full text Cite

Sex in fungi.

Journal Article Annu Rev Genet · 2011 Sexual reproduction enables genetic exchange in eukaryotic organisms as diverse as fungi, animals, plants, and ciliates. Given its ubiquity, sex is thought to have evolved once, possibly concomitant with or shortly after the origin of eukaryotic organisms ... Full text Link to item Cite

Comparative and functional genomics provide insights into the pathogenicity of dermatophytic fungi.

Journal Article Genome Biol · 2011 BACKGROUND: Millions of humans and animals suffer from superficial infections caused by a group of highly specialized filamentous fungi, the dermatophytes, which exclusively infect keratinized host structures. To provide broad insights into the molecular b ... Full text Link to item Cite

Genome variation in Cryptococcus gattii, an emerging pathogen of immunocompetent hosts.

Journal Article mBio · 2011 Cryptococcus gattii recently emerged as the causative agent of cryptococcosis in healthy individuals in western North America, despite previous characterization of the fungus as a pathogen in tropical or subtropical regions. As a foundation to study the ge ... Full text Link to item Cite

Structure, function, and phylogeny of the mating locus in the Rhizopus oryzae complex.

Journal Article PLoS One · December 9, 2010 The Rhizopus oryzae species complex is a group of zygomycete fungi that are common, cosmopolitan saprotrophs. Some strains are used beneficially for production of Asian fermented foods but they can also act as opportunistic human pathogens. Although R. ory ... Full text Open Access Link to item Cite

On the roles of calcineurin in fungal growth and pathogenesis

Journal Article Current Fungal Infection Reports · December 1, 2010 Calcineurin is a calcium-activated phosphatase that controls morphogenesis and stress responses in eukaryotes. Fungal pathogens have adopted the calcineurin pathway to survive and effectively propagate within the host. The difficulty in treating fungal inf ... Full text Cite

Characterizing the role of RNA silencing components in Cryptococcus neoformans.

Journal Article Fungal Genet Biol · December 2010 The RNA interference (RNAi) mediated by homology-dependent degradation of the target mRNA with small RNA molecules plays a key role in controlling transcription and translation processes in a number of eukaryotic organisms. The RNAi machinery is also evolu ... Full text Link to item Cite

Sex-induced silencing defends the genome of Cryptococcus neoformans via RNAi.

Journal Article Genes Dev · November 15, 2010 Cosuppression is a silencing phenomenon triggered by the introduction of homologous DNA sequences into the genomes of organisms as diverse as plants, fungi, flies, and nematodes. Here we report sex-induced silencing (SIS), which is triggered by tandem inte ... Full text Link to item Cite

Conservation, duplication, and loss of the Tor signaling pathway in the fungal kingdom.

Journal Article BMC Genomics · September 23, 2010 BACKGROUND: The nutrient-sensing Tor pathway governs cell growth and is conserved in nearly all eukaryotic organisms from unicellular yeasts to multicellular organisms, including humans. Tor is the target of the immunosuppressive drug rapamycin, which in c ... Full text Open Access Link to item Cite

Comparative transcriptome analysis of the CO2 sensing pathway via differential expression of carbonic anhydrase in Cryptococcus neoformans.

Journal Article Genetics · August 2010 Carbon dioxide (CO(2)) sensing and metabolism via carbonic anhydrases (CAs) play pivotal roles in survival and proliferation of pathogenic fungi infecting human hosts from natural environments due to the drastic difference in CO(2) levels. In Cryptococcus ... Full text Link to item Cite

Ferrochelatase is a conserved downstream target of the blue light-sensing White collar complex in fungi.

Journal Article Microbiology (Reading) · August 2010 Light is a universal signal perceived by organisms, including fungi, in which light regulates common and unique biological processes depending on the species. Previous research has established that conserved proteins, originally called White collar 1 and 2 ... Full text Open Access Link to item Cite

Evolution of eukaryotic microbial pathogens via covert sexual reproduction.

Journal Article Cell Host Microbe · July 22, 2010 Sexual reproduction enables eukaryotic organisms to reassort genetic diversity and purge deleterious mutations, producing better-fit progeny. Sex arose early and pervades eukaryotes. Fungal and parasite pathogens once thought asexual have maintained crypti ... Full text Link to item Cite

Cryptococcal cell morphology affects host cell interactions and pathogenicity.

Journal Article PLoS Pathog · June 17, 2010 Cryptococcus neoformans is a common life-threatening human fungal pathogen. The size of cryptococcal cells is typically 5 to 10 microm. Cell enlargement was observed in vivo, producing cells up to 100 microm. These morphological changes in cell size affect ... Full text Open Access Link to item Cite

Surfactant protein D binding to Aspergillus fumigatus hyphae is calcineurin-sensitive.

Journal Article Med Mycol · June 2010 Surfactant protein D (SP-D) plays a central role in pulmonary innate immune responses to microbes and allergens, often enhancing clearance of inhaled material. Although SP-D functions during bacterial and viral infections are well established, much less is ... Full text Link to item Cite

The evolution of sex: a perspective from the fungal kingdom.

Journal Article Microbiol Mol Biol Rev · June 2010 Sex is shrouded in mystery. Not only does it preferentially occur in the dark for both fungi and many animals, but evolutionary biologists continue to debate its benefits given costs in light of its pervasive nature. Experimental studies of the benefits an ... Full text Link to item Cite

The mating type locus (MAT) and sexual reproduction of Cryptococcus heveanensis: insights into the evolution of sex and sex-determining chromosomal regions in fungi.

Journal Article PLoS Genet · May 20, 2010 Mating in basidiomycetous fungi is often controlled by two unlinked, multiallelic loci encoding homeodomain transcription factors or pheromones/pheromone receptors. In contrast to this tetrapolar organization, Cryptococcus neoformans/Cryptococcus gattii ha ... Full text Open Access Link to item Cite

Role of an expanded inositol transporter repertoire in Cryptococcus neoformans sexual reproduction and virulence.

Journal Article mBio · May 18, 2010 Cryptococcus neoformans and Cryptococcus gattii are globally distributed human fungal pathogens and the leading causes of fungal meningitis. Recent studies reveal that myo-inositol is an important factor for fungal sexual reproduction. That C. neoformans c ... Full text Link to item Cite

Transcription factors Mat2 and Znf2 operate cellular circuits orchestrating opposite- and same-sex mating in Cryptococcus neoformans.

Journal Article PLoS Genet · May 13, 2010 Cryptococcus neoformans is a human fungal pathogen that undergoes a dimorphic transition from a unicellular yeast to multicellular hyphae during opposite sex (mating) and unisexual reproduction (same-sex mating). Opposite- and same-sex mating are induced b ... Full text Open Access Link to item Cite

Evolution of the sex-related locus and genomic features shared in microsporidia and fungi.

Journal Article PLoS One · May 7, 2010 BACKGROUND: Microsporidia are obligate intracellular, eukaryotic pathogens that infect a wide range of animals from nematodes to humans, and in some cases, protists. The preponderance of evidence as to the origin of the microsporidia reveals a close relati ... Full text Open Access Link to item Cite

Emergence and pathogenicity of highly virulent Cryptococcus gattii genotypes in the northwest United States.

Journal Article PLoS Pathog · April 22, 2010 Cryptococcus gattii causes life-threatening disease in otherwise healthy hosts and to a lesser extent in immunocompromised hosts. The highest incidence for this disease is on Vancouver Island, Canada, where an outbreak is expanding into neighboring regions ... Full text Link to item Cite

Morphological and genomic characterization of Filobasidiella depauperata: a homothallic sibling species of the pathogenic cryptococcus species complex.

Journal Article PLoS One · March 10, 2010 The fungal species Cryptococcus neoformans and Cryptococcus gattii cause respiratory and neurological disease in animals and humans following inhalation of basidiospores or desiccated yeast cells from the environment. Sexual reproduction in C. neoformans a ... Full text Open Access Link to item Cite

Comparative transcriptome analysis reveals novel roles of the Ras and cyclic AMP signaling pathways in environmental stress response and antifungal drug sensitivity in Cryptococcus neoformans.

Journal Article Eukaryot Cell · March 2010 The cyclic AMP (cAMP) pathway plays a central role in the growth, differentiation, and virulence of pathogenic fungi, including Cryptococcus neoformans. Three upstream signaling regulators of adenylyl cyclase (Cac1), Ras, Aca1, and Gpa1, have been demonstr ... Full text Link to item Cite

Elucidating the Candida albicans calcineurin signaling cascade controlling stress response and virulence.

Journal Article Fungal Genet Biol · February 2010 The protein phosphatase calcineurin is a key mediator of virulence and antifungal susceptibility of multiple fungal pathogens including Candida albicans, Cryptococcus neoformans, and Aspergillus fumigatus, and has clinical potential as a therapeutic target ... Full text Link to item Cite

Septins enforce morphogenetic events during sexual reproduction and contribute to virulence of Cryptococcus neoformans.

Journal Article Mol Microbiol · February 2010 Septins are conserved, cytoskeletal GTPases that contribute to cytokinesis, exocytosis, cell surface organization and vesicle fusion by mechanisms that are poorly understood. Roles of septins in morphogenesis and virulence of a human pathogen and basidiomy ... Full text Link to item Cite

Transcription factors Mat2 and Znf2 operate cellular circuits orchestrating opposite- and same-sex mating in Cryptococcus neoformans.

Journal Article PLoS genetics · 2010 Cryptococcus neoformans is a human fungal pathogen that undergoes a dimorphic transition from a unicellular yeast to multicellular hyphae during opposite sex (mating) and unisexual reproduction (same-sex mating). Opposite- and same-sex mating are induced b ... Full text Cite

The mating type locus (MAT) and sexual reproduction of Cryptococcus heveanensis: insights into the evolution of sex and sex-determining chromosomal regions in fungi.

Journal Article PLoS genetics · 2010 Mating in basidiomycetous fungi is often controlled by two unlinked, multiallelic loci encoding homeodomain transcription factors or pheromones/pheromone receptors. In contrast to this tetrapolar organization, Cryptococcus neoformans/Cryptococcus gattii ha ... Full text Cite

Organization and evolutionary trajectory of the mating type (MAT) locus in dermatophyte and dimorphic fungal pathogens.

Journal Article Eukaryot Cell · January 2010 Sexual reproduction in fungi is governed by a specialized genomic region, the mating type (MAT) locus, whose gene identity, organization, and complexity are diverse. We identified the MAT locus of five dermatophyte fungal pathogens (Microsporum gypseum, Mi ... Full text Link to item Cite

Spores as infectious propagules of Cryptococcus neoformans.

Journal Article Infect Immun · October 2009 Cryptococcus neoformans and Cryptococcus gattii are closely related pathogenic fungi that cause pneumonia and meningitis in both immunocompromised and immunocompetent hosts and are a significant global infectious disease risk. Both species are found in the ... Full text Link to item Cite

Generation of genetic diversity in microsporidia via sexual reproduction and horizontal gene transfer.

Journal Article Commun Integr Biol · September 2009 Microsporidia are obligate intracellular pathogens mainly infecting both vertebrate and invertebrate hosts. The group comprises approximately 150 genera with 1,200 species. Due to sequence divergence phylogenic reconstructions that are solely based on DNA ... Full text Link to item Cite

Remodeling of global transcription patterns of Cryptococcus neoformans genes mediated by the stress-activated HOG signaling pathways.

Journal Article Eukaryot Cell · August 2009 The ability to sense and adapt to a hostile host environment is a crucial element for virulence of pathogenic fungi, including Cryptococcus neoformans. These cellular responses are evoked by diverse signaling cascades, including the stress-activated HOG pa ... Full text Link to item Cite

Spread of Cryptococcus gattii into Pacific Northwest region of the United States.

Journal Article Emerg Infect Dis · August 2009 Cryptococcus gattii has emerged as a human and animal pathogen in the Pacific Northwest. First recognized on Vancouver Island, British Columbia, Canada, it now involves mainland British Columbia, and Washington and Oregon in the United States. In Canada, t ... Full text Link to item Cite

Surfactant protein D increases phagocytosis of hypocapsular Cryptococcus neoformans by murine macrophages and enhances fungal survival.

Journal Article Infect Immun · July 2009 Cryptococcus neoformans is a facultative intracellular opportunistic pathogen and the leading cause of fungal meningitis in humans. In the absence of a protective cellular immune response, the inhalation of C. neoformans cells or spores results in pulmonar ... Full text Link to item Cite

First reported case of Cryptococcus gattii in the Southeastern USA: implications for travel-associated acquisition of an emerging pathogen.

Journal Article PLoS One · June 10, 2009 In 2007, the first confirmed case of Cryptococcus gattii was reported in the state of North Carolina, USA. An otherwise healthy HIV negative male patient presented with a large upper thigh cryptococcoma in February, which was surgically removed and the pat ... Full text Link to item Cite

Mechanistic plasticity of sexual reproduction and meiosis in the Candida pathogenic species complex.

Journal Article Curr Biol · June 9, 2009 BACKGROUND: Candida species are microbial pathogens originally thought to be asexual, but several are now recognized as sexual or parasexual. Candida albicans, the most common fungus infecting humans, is an obligate diploid with a parasexual cycle involvin ... Full text Link to item Cite

Evolution of pathogenicity and sexual reproduction in eight Candida genomes.

Journal Article Nature · June 4, 2009 Candida species are the most common cause of opportunistic fungal infection worldwide. Here we report the genome sequences of six Candida species and compare these and related pathogens and non-pathogens. There are significant expansions of cell wall, secr ... Full text Link to item Cite

A constitutively active GPCR governs morphogenic transitions in Cryptococcus neoformans.

Journal Article EMBO J · May 6, 2009 Sex in fungi is driven by peptide pheromones sensed through seven-transmembrane pheromone receptors. In Cryptococcus neoformans, sexual reproduction occurs through an outcrossing/heterothallic a- sexual cycle or an inbreeding/homothallic - unisexual mating ... Full text Link to item Cite

Hsp90 orchestrates temperature-dependent Candida albicans morphogenesis via Ras1-PKA signaling.

Journal Article Curr Biol · April 28, 2009 BACKGROUND: Hsp90 is an environmentally contingent molecular chaperone that influences the form and function of diverse regulators of cellular signaling. Hsp90 potentiates the evolution of fungal drug resistance by enabling crucial cellular stress response ... Full text Link to item Cite

Phycomyces MADB interacts with MADA to form the primary photoreceptor complex for fungal phototropism.

Journal Article Proc Natl Acad Sci U S A · April 28, 2009 The fungus Phycomyces blakesleeanus reacts to environmental signals, including light, gravity, touch, and the presence of nearby objects, by changing the speed and direction of growth of its fruiting body (sporangiophore). Phototropism, growth toward light ... Full text Link to item Cite

Molecular evidence that the range of the Vancouver Island outbreak of Cryptococcus gattii infection has expanded into the Pacific Northwest in the United States.

Journal Article J Infect Dis · April 1, 2009 Cryptococcus neoformans frequently causes fungal meningitis in immunocompromised patients, whereas the related species C. gattii is restricted to tropical and subtropical regions,where it usually infects immunocompetent individuals.An outbreak of C. gattii ... Full text Link to item Cite

Aspergillus fumigatus calcipressin CbpA is involved in hyphal growth and calcium homeostasis.

Journal Article Eukaryot Cell · April 2009 Calcineurin is a conserved protein phosphatase that plays a critical role in Ca(2+) signaling and stress responses. Previously, a new class of conserved calcineurin-binding proteins, the calcipressins, was identified. However, the role of these proteins re ... Full text Link to item Cite

Dynamic duo takes down fungal villains.

Journal Article Proc Natl Acad Sci U S A · March 3, 2009 Full text Link to item Cite

Phylogeny and phenotypic characterization of pathogenic Cryptococcus species and closely related saprobic taxa in the Tremellales.

Journal Article Eukaryot Cell · March 2009 The basidiomycetous yeasts Cryptococcus neoformans and Cryptococcus gattii are closely related sibling species that cause respiratory and neurological disease in humans and animals. Within these two recognized species, phylogenetic analysis reveals at leas ... Full text Link to item Cite

Identification of ENA1 as a virulence gene of the human pathogenic fungus Cryptococcus neoformans through signature-tagged insertional mutagenesis.

Journal Article Eukaryot Cell · March 2009 A library of more than 4,500 signature-tagged insertion mutants of the human pathogenic fungus Cryptococcus neoformans was generated, and a subset was screened in a murine inhalation model to identify genes required for virulence. New genes that regulate a ... Full text Link to item Cite

Signalling pathways in the pathogenesis of Cryptococcus.

Journal Article Cell Microbiol · March 2009 Efficient communication with the environment is critical for all living organisms. Fungi utilize complex signalling systems to sense their environments and control proliferation, development and in some cases virulence. Well-studied signalling pathways inc ... Full text Link to item Cite

The protein kinase Tor1 regulates adhesin gene expression in Candida albicans.

Journal Article PLoS Pathog · February 2009 Eukaryotic cell growth is coordinated in response to nutrient availability, growth factors, and environmental stimuli, enabling cell-cell interactions that promote survival. The rapamycin-sensitive Tor1 protein kinase, which is conserved from yeasts to hum ... Full text Link to item Cite

Trimorphic stepping stones pave the way to fungal virulence.

Journal Article Proc Natl Acad Sci U S A · January 13, 2009 Full text Link to item Cite

Diploids in the Cryptococcus neoformans serotype A population homozygous for the alpha mating type originate via unisexual mating.

Journal Article PLoS Pathog · January 2009 The ubiquitous environmental human pathogen Cryptococcus neoformans is traditionally considered a haploid fungus with a bipolar mating system. In nature, the alpha mating type is overwhelmingly predominant over a. How genetic diversity is generated and mai ... Full text Link to item Cite

Loss of allergen 1 confers a hypervirulent phenotype that resembles mucoid switch variants of Cryptococcus neoformans.

Journal Article Infect Immun · January 2009 Microbial survival in a host is usually dependent on the ability of a pathogen to undergo changes that promote escape from host defense mechanisms. The human-pathogenic fungus Cryptococcus neoformans undergoes phenotypic switching in vivo that promotes per ... Full text Link to item Cite

Cryptococcus gattii with bimorphic colony types in a dog in western Oregon: additional evidence for expansion of the Vancouver Island outbreak.

Journal Article J Vet Diagn Invest · January 2009 Cryptococcus gattii was isolated from a 1.5-year-old dog with systemic cryptococcosis in Oregon. The dog had no link to Vancouver Island or British Columbia, Canada. Samples from a nasal swab and from a granulomatous mass within the cranial cavity were poo ... Full text Link to item Cite

Orchestration of sexual reproduction and virulence by the fungal mating-type locus.

Journal Article Curr Opin Microbiol · December 2008 The mating-type locus (MAT) orchestrates sexual reproduction in fungi. Sexual reproduction is related not only to fitness of an organism, but also correlated with virulence in certain pathogens. In the dandruff-associated fungus Malassesia globosa, althoug ... Full text Link to item Cite

Microsporidia evolved from ancestral sexual fungi.

Journal Article Curr Biol · November 11, 2008 Microsporidia are obligate, intracellular eukaryotic pathogens that infect animal cells, including humans [1]. Previous studies suggested microsporidia share a common ancestor with fungi [2-7]. However, the exact nature of this phylogenetic relationship is ... Full text Link to item Cite

Magnificent seven: roles of G protein-coupled receptors in extracellular sensing in fungi.

Journal Article FEMS Microbiol Rev · November 2008 G protein-coupled receptors (GPCRs) represent the largest family of transmembrane receptors and are responsible for transducing extracellular signals into intracellular responses that involve complex intracellular-signaling networks. This review highlights ... Full text Link to item Cite

Transitions in sexuality: recapitulation of an ancestral tri- and tetrapolar mating system in Cryptococcus neoformans.

Journal Article Eukaryot Cell · October 2008 Sex is orchestrated by the mating-type locus (MAT) in fungi and by sex chromosomes in plants and animals. In fungi, two patterns of sexuality occur: bipolar with a single, typically biallelic sex determinant that promotes inbreeding, and tetrapolar with tw ... Full text Link to item Cite

Isolates of Cryptococcus neoformans from infected animals reveal genetic exchange in unisexual, alpha mating type populations.

Journal Article Eukaryot Cell · October 2008 Sexual reproduction and genetic exchange are important for the evolution of fungal pathogens and for producing potentially infective spores. Studies to determine whether sex occurs in the pathogenic yeast Cryptococcus neoformans var. grubii have produced e ... Full text Link to item Cite

The RGS protein Crg2 regulates both pheromone and cAMP signalling in Cryptococcus neoformans.

Journal Article Mol Microbiol · October 2008 G proteins orchestrate critical cellular functions by transducing extracellular signals into internal signals and controlling cellular responses to environmental cues. G proteins typically function as switches that are activated by G protein-coupled recept ... Full text Link to item Cite

Central nervous system cryptococcosis in solid organ transplant recipients: clinical relevance of abnormal neuroimaging findings.

Journal Article Transplantation · September 15, 2008 BACKGROUND: Prognostic implications of cryptococcal antigen and outcomes associated with central nervous system (CNS) cryptococcal lesions in solid organ transplant recipients have not been fully defined. METHODS: Patients were derived form a cohort of 122 ... Full text Link to item Cite

Calcineurin localizes to the hyphal septum in Aspergillus fumigatus: implications for septum formation and conidiophore development.

Journal Article Eukaryot Cell · September 2008 A functional calcineurin A fusion to enhanced green fluorescent protein (EGFP), CnaA-EGFP, was expressed in the Aspergillus fumigatus DeltacnaA mutant. CnaA-EGFP localized in actively growing hyphal tips, at the septa, and at junctions between the vesicle ... Full text Link to item Cite

Signaling cascades as drug targets in model and pathogenic fungi.

Journal Article Curr Opin Investig Drugs · August 2008 Microbes evolved to produce natural products that inhibit growth of competing soil microorganisms. In many cases these compounds act on fungi, which are eukaryotes with conserved gene sequences closely related to metazoans, including humans. The calcineuri ... Link to item Cite

Calcineurin target CrzA regulates conidial germination, hyphal growth, and pathogenesis of Aspergillus fumigatus.

Journal Article Eukaryot Cell · July 2008 The calcineurin pathway is a critical signal transduction pathway in fungi that mediates growth, morphology, stress responses, and pathogenicity. The importance of the calcineurin pathway in fungal physiology creates an opportunity for the development of n ... Full text Link to item Cite

A Mep2-dependent transcriptional profile links permease function to gene expression during pseudohyphal growth in Saccharomyces cerevisiae.

Journal Article Mol Biol Cell · July 2008 The ammonium permease Mep2 is required for the induction of pseudohyphal growth, a process in Saccharomyces cerevisiae that occurs in response to nutrient limitation. Mep2 has both a transport and a regulatory function, supporting models in which Mep2 acts ... Full text Link to item Cite

Impact of mating type, serotype, and ploidy on the virulence of Cryptococcus neoformans.

Journal Article Infect Immun · July 2008 Hybridization with polyploidization is a significant biological force driving evolution. The effect of combining two distinct genomes in one organism on the virulence potential of pathogenic fungi is not clear. Cryptococcus neoformans, the most common caus ... Full text Link to item Cite

Synergistic effect of calcineurin inhibitors and fluconazole against Candida albicans biofilms.

Journal Article Antimicrob Agents Chemother · March 2008 Calcineurin is a Ca2+-calmodulin-activated serine/threonine-specific protein phosphatase that governs multiple aspects of fungal physiology, including cation homeostasis, morphogenesis, antifungal drug susceptibility, and virulence. Growth of Candida albic ... Full text Link to item Cite

Calcineurin inhibitor agents interact synergistically with antifungal agents in vitro against Cryptococcus neoformans isolates: correlation with outcome in solid organ transplant recipients with cryptococcosis.

Journal Article Antimicrob Agents Chemother · February 2008 Synergistic interactions were observed between CIs and antifungal agents against 53 (90%) of 59 Cryptococcus neoformans isolates from solid organ transplant recipients with cryptococcosis and may account for better outcomes in patients with cryptococcosis ... Full text Link to item Cite

Fungal genome sequencing and bioenergy

Journal Article Fungal Biology Reviews · February 1, 2008 To date, the number of ongoing filamentous fungal genome sequencing projects is almost tenfold fewer than those of bacterial and archaeal genome projects. The fungi chosen for sequencing represent narrow kingdom diversity; most are pathogens or models. We ... Full text Cite

Impact of ammonium permeases mepA, mepB, and mepC on nitrogen-regulated secondary metabolism in Fusarium fujikuroi.

Journal Article Eukaryot Cell · February 2008 In Fusarium fujikuroi, the production of gibberellins and bikaverin is repressed by nitrogen sources such as glutamine or ammonium. Sensing and uptake of ammonium by specific permeases play key roles in nitrogen metabolism. Here, we describe the cloning of ... Full text Link to item Cite

Amt2 permease is required to induce ammonium-responsive invasive growth and mating in Cryptococcus neoformans.

Journal Article Eukaryot Cell · February 2008 The conserved AmtB/Mep/Rh family of proteins mediate the transport of ammonium across cellular membranes in a wide range of organisms. Certain fungal members of this group are required to initiate filamentous growth. We have investigated the functions of t ... Full text Link to item Cite

Fungal horizons: the Asilomar Fungal Genetics Conference 2007.

Journal Article Fungal Genet Biol · February 2008 This meeting report covers advances presented at the 2007 Asilomar Fungal Genetics Conference that expand our understanding of fungal biology and the myriad ways in which studies of organisms in this ubiquitous and successful kingdom of life advance an und ... Full text Link to item Cite

Pulmonary cryptococcosis in solid organ transplant recipients: clinical relevance of serum cryptococcal antigen.

Journal Article Clin Infect Dis · January 15, 2008 BACKGROUND: The role of serum cryptococcal antigen in the diagnosis and determinants of antigen positivity in solid organ transplant (SOT) recipients with pulmonary cryptococcosis has not been fully defined. METHODS: We conducted a prospective, multicenter ... Full text Link to item Cite

Identification of the sex genes in an early diverged fungus.

Journal Article Nature · January 10, 2008 Sex determination in fungi is controlled by a small, specialized region of the genome in contrast to the large sex-specific chromosomes of animals and some plants. Different gene combinations reside at these mating-type (MAT) loci and confer sexual identit ... Full text Link to item Cite

Yeast as a tool in cancer research

Journal Article Yeast as a Tool in Cancer Research · December 1, 2007 Yeast is an experimental system that has led to critical discoveries in cell and molecular biology. The wide range of tools available in yeast has also made it an important system in many areas relevant to cancer including anti-cancer drug discovery, mecha ... Full text Cite

Ssk2 mitogen-activated protein kinase kinase kinase governs divergent patterns of the stress-activated Hog1 signaling pathway in Cryptococcus neoformans.

Journal Article Eukaryot Cell · December 2007 The stress-activated p38/Hog1 mitogen-activated protein kinase (MAPK) pathway is structurally conserved in many diverse organisms, including fungi and mammals, and modulates myriad cellular functions. The Hog1 pathway is uniquely specialized to control dif ... Full text Link to item Cite

alpha AD alpha hybrids of Cryptococcus neoformans: evidence of same-sex mating in nature and hybrid fitness.

Journal Article PLoS Genet · October 2007 Cryptococcus neoformans is a ubiquitous human fungal pathogen that causes meningoencephalitis in predominantly immunocompromised hosts. The fungus is typically haploid, and sexual reproduction involves two individuals with opposite mating types/sexes, alph ... Full text Link to item Cite

Targeting the calcineurin pathway enhances ergosterol biosynthesis inhibitors against Trichophyton mentagrophytes in vitro and in a human skin infection model.

Journal Article Antimicrob Agents Chemother · October 2007 Fluconazole-FK506 or fluconazole-cyclosporine drug combinations were tested in an ex vivo Trichophyton mentagrophytes human skin infection model. Conidia colonization was monitored by scanning electron microscopy over a 7-day treatment period. The fluconaz ... Full text Link to item Cite

First contemporary case of human infection with Cryptococcus gattii in Puget Sound: evidence for spread of the Vancouver Island outbreak.

Journal Article J Clin Microbiol · September 2007 We report a case of cryptococcosis due to C. gattii which appears to have been acquired in the Puget Sound region, Washington State. Genotyping confirmed identity to the predominant Vancouver Island genotype. This is the first documented case of human dise ... Full text Link to item Cite

G protein signaling governing cell fate decisions involves opposing Galpha subunits in Cryptococcus neoformans.

Journal Article Mol Biol Cell · September 2007 Communication between cells and their environments is often mediated by G protein-coupled receptors and cognate G proteins. In fungi, one such signaling cascade is the mating pathway triggered by pheromone/pheromone receptor recognition. Unlike Saccharomyc ... Full text Link to item Cite

Many globally isolated AD hybrid strains of Cryptococcus neoformans originated in Africa.

Journal Article PLoS Pathog · August 17, 2007 Interspecific and intervarietal hybridization may contribute to the biological diversity of fungal populations. Cryptococcus neoformans is a pathogenic yeast and the most common fungal cause of meningitis in patients with AIDS. Most patients are infected w ... Full text Link to item Cite

The virulence of human pathogenic fungi: notes from the South of France.

Journal Article Cell Host Microbe · August 16, 2007 The Second FEBS Advanced Lecture Course on Human Fungal Pathogens: Molecular Mechanisms of Host-Pathogen Interactions and Virulence, organized by Christophe d'Enfert (Institut Pasteur, France), Anita Sil (UCSF, USA), and Steffen Rupp (Fraunhofer, IGB, Germ ... Full text Link to item Cite

Calcineurin inhibition or mutation enhances cell wall inhibitors against Aspergillus fumigatus.

Journal Article Antimicrob Agents Chemother · August 2007 Calcineurin mutation or inhibition enhanced the antifungal morphological effect of cell wall inhibitors caspofungin or nikkomycin Z against Aspergillus fumigatus. Quantification of 1,3-beta-d-glucan revealed decreased amounts in the calcineurin A (Deltacna ... Full text Link to item Cite

Many globally isolated AD hybrid strains of Cryptococcus neoformans originated in Africa

Journal Article PLoS Pathogens · August 1, 2007 Interspecific and intervarietal hybridization may contribute to the biological diversity of fungal populations. Cryptococcus neoformans is a pathogenic yeast and the most common fungal cause of meningitis in patients with AIDS. Most patients are infected w ... Full text Cite

Eca1, a sarcoplasmic/endoplasmic reticulum Ca2+-ATPase, is involved in stress tolerance and virulence in Cryptococcus neoformans.

Journal Article Infect Immun · July 2007 The basidiomycetous fungal pathogen Cryptococcus neoformans is adapted to survive challenges in the soil and environment and within the unique setting of the mammalian host. A C. neoformans mutant was isolated with enhanced virulence in a soil amoeba model ... Full text Link to item Cite

The human fungal pathogen Cryptococcus can complete its sexual cycle during a pathogenic association with plants.

Journal Article Cell Host Microbe · June 14, 2007 Cryptococcus is a globally distributed human fungal pathogen that primarily afflicts immunocompromised individuals. How and why this human fungal pathogen associates with plants and how this environmental niche influences its life cycle remains a mystery. ... Full text Link to item Cite

Endosymbiosis: the evil within.

Journal Article Curr Biol · June 5, 2007 A recent study has revealed a novel feature of the symbiosis between a bacterium and a fungal pathogen. In addition to producing a pathogenic toxin, the endosymbiont of the rice pathogen Rhizopus microsporus controls the ability of the fungus to form spora ... Full text Link to item Cite

Harnessing calcineurin as a novel anti-infective agent against invasive fungal infections.

Journal Article Nat Rev Microbiol · June 2007 The number of immunocompromised patients with invasive fungal infections continues to increase and new antifungal therapies are not keeping pace with the growing incidence of these infections and their associated mortality. Calcineurin inhibition is curren ... Full text Link to item Cite

Cryptococcus neoformans mates on pigeon guano: implications for the realized ecological niche and globalization.

Journal Article Eukaryot Cell · June 2007 The ecological niche that a species can occupy is determined by its resource requirements and the physical conditions necessary for survival. The niche to which an organism is most highly adapted is the realized niche, whereas the complete range of habitat ... Full text Link to item Cite

An EcoRI-RsrI chimeric restriction endonuclease retains parental sequence specificity.

Journal Article Biochim Biophys Acta · May 2007 To test their structural and functional similarity, hybrids were constructed between EcoRI and RsrI, two restriction endonucleases recognizing the same DNA sequence and sharing 50% amino acid sequence identity. One of the chimeric proteins (EERE), in which ... Full text Link to item Cite

Evolution of the mating type locus: insights gained from the dimorphic primary fungal pathogens Histoplasma capsulatum, Coccidioides immitis, and Coccidioides posadasii.

Journal Article Eukaryot Cell · April 2007 Sexual reproduction of fungi is governed by the mating type (MAT) locus, a specialized region of the genome encoding key transcriptional regulators that direct regulatory networks to specify cell identity and fate. Knowledge of MAT locus structure and evol ... Full text Link to item Cite

Cryptococcus neoformans in organ transplant recipients: impact of calcineurin-inhibitor agents on mortality.

Journal Article J Infect Dis · March 1, 2007 Variables influencing the risk of dissemination and outcome of Cryptococcus neoformans infection were assessed in 111 organ transplant recipients with cryptococcosis in a prospective, multicenter, international study. Sixty-one percent (68/111) of the pati ... Full text Link to item Cite

The mating type-specific homeodomain genes SXI1 alpha and SXI2a coordinately control uniparental mitochondrial inheritance in Cryptococcus neoformans.

Journal Article Curr Genet · March 2007 In the great majority of sexual eukaryotes, mitochondrial genomes are inherited almost exclusively from a single parent. While many hypotheses have been proposed to explain this phenomenon, very little is known about the genetic elements controlling unipar ... Full text Link to item Cite

Divergence of protein kinase A catalytic subunits in Cryptococcus neoformans and Cryptococcus gattii illustrates evolutionary reconfiguration of a signaling cascade.

Journal Article Eukaryot Cell · March 2007 Gene duplication and divergence via both the loss and gain of gene activities are powerful evolutionary forces underlying the origin of new biological functions. Here a comparative genetics approach was applied to examine the roles of protein kinase A (PKA ... Full text Link to item Cite

Fungal pathogenesis: gene clusters unveiled as secrets within the Ustilago maydis code.

Journal Article Curr Biol · February 6, 2007 The genome sequence of a second plant pathogenic fungus is now available, revealing unique gene clusters encoding secretory proteins that are induced during infection and regulate pathogenesis. Gene clusters play important roles in pathogenic fungi, yet th ... Full text Link to item Cite

Sensing the environment: lessons from fungi.

Journal Article Nat Rev Microbiol · January 2007 All living organisms use numerous signal-transduction systems to sense and respond to their environments and thereby survive and proliferate in a range of biological niches. Molecular dissection of these signalling networks has increased our understanding ... Full text Link to item Cite

Sex and virulence of human pathogenic fungi.

Journal Article Adv Genet · 2007 Over the past decade, opportunistic fungal infectious diseases have increased in prevalence as the population of immunocompromised individuals escalated due to HIV/AIDS and immunosuppression associated with organ transplantation and cancer therapies. In th ... Full text Link to item Cite

Peroxisome function regulates growth on glucose in the basidiomycete fungus Cryptococcus neoformans.

Journal Article Eukaryot Cell · January 2007 The function of the peroxisomes was examined in the pathogenic basidiomycete Cryptococcus neoformans. Recent studies reveal the glyoxylate pathway is required for virulence of diverse microbial pathogens of plants and animals. One exception is C. neoforman ... Full text Link to item Cite

Unique applications of novel antifungal drug combinations

Journal Article Anti-Infective Agents in Medicinal Chemistry · January 1, 2007 Candida albicans is a commensal fungal organism that can over-proliferate and cause disease in the appropriate host setting. C. albicans can cause irritating superficial skin and mucocutaneous infections such as diaper rash and vaginal yeast infections, re ... Full text Cite

Eukaryotes

Journal Article Current Opinion in Microbiology · December 1, 2006 Full text Cite

Virulence attributes and hyphal growth of C. neoformans are quantitative traits and the MATalpha allele enhances filamentation.

Journal Article PLoS Genet · November 17, 2006 Cryptococcus neoformans is a fungal human pathogen with a bipolar mating system. It undergoes a dimorphic transition from a unicellular yeast to hyphal filamentous growth during mating and monokaryotic fruiting. The traditional sexual cycle that leads to t ... Full text Link to item Cite

Recombination hotspots flank the Cryptococcus mating-type locus: implications for the evolution of a fungal sex chromosome.

Journal Article PLoS Genet · November 3, 2006 Recombination increases dramatically during meiosis to promote genetic exchange and generate recombinant progeny. Interestingly, meiotic recombination is unevenly distributed throughout genomes, and, as a consequence, genetic and physical map distances do ... Full text Link to item Cite

Virulence attributes and hyphal growth of C. neoformans are quantitative traits and the MATα allele enhances filamentation

Journal Article PLoS Genetics · November 1, 2006 Cryptococcus neoformans is a fungal human pathogen with a bipolar mating system. It undergoes a dimorphic transition from a unicellular yeast to hyphal filamentous growth during mating and monokaryotic fruiting. The traditional sexual cycle that leads to t ... Full text Cite

Calcineurin promotes infection of the cornea by Candida albicans and can be targeted to enhance fluconazole therapy.

Journal Article Antimicrob Agents Chemother · November 2006 In an established Candida albicans murine keratitis model, combination therapy with ophthalmic preparations of fluconazole and cyclosporine A (CsA) demonstrated in vivo drug synergy and effectively resolved wild-type C. albicans infection more rapidly than ... Full text Link to item Cite

Sexual reproduction and the evolution of microbial pathogens.

Journal Article Curr Biol · September 5, 2006 Three common systemic human fungal pathogens--Cryptococcus neoformans, Candida albicans and Aspergillus fumigatus--have retained all the machinery to engage in sexual reproduction, and yet their populations are often clonal with limited evidence for recomb ... Full text Link to item Cite

Conserved elements of the RAM signaling pathway establish cell polarity in the basidiomycete Cryptococcus neoformans in a divergent fashion from other fungi.

Journal Article Mol Biol Cell · September 2006 In eukaryotes the complex processes of development, differentiation, and proliferation require carefully orchestrated changes in cellular morphology. Single-celled eukaryotes provide tractable models for the elucidation of signaling pathways involved in mo ... Full text Link to item Cite

A unique fungal two-component system regulates stress responses, drug sensitivity, sexual development, and virulence of Cryptococcus neoformans.

Journal Article Mol Biol Cell · July 2006 The stress-activated mitogen-activated protein kinase (MAPK) pathway is widely used by eukaryotic organisms as a central conduit via which cellular responses to the environment effect growth and differentiation. The basidiomycetous human fungal pathogen Cr ... Full text Link to item Cite

Calcineurin controls growth, morphology, and pathogenicity in Aspergillus fumigatus.

Journal Article Eukaryot Cell · July 2006 Calcineurin is implicated in a myriad of human diseases as well as homeostasis and virulence in several major human pathogenic microorganisms. The fungus Aspergillus fumigatus is a leading cause of infectious death in the rapidly expanding immunocompromise ... Full text Link to item Cite

The kelch proteins Gpb1 and Gpb2 inhibit Ras activity via association with the yeast RasGAP neurofibromin homologs Ira1 and Ira2.

Journal Article Mol Cell · June 23, 2006 The G protein-coupled receptor Gpr1 and associated Galpha subunit Gpa2 govern dimorphic transitions in response to extracellular nutrients by signaling coordinately with Ras to activate adenylyl cyclase in the yeast Saccharomyces cerevisiae. Gpa2 forms a p ... Full text Link to item Cite

Yeast diversity sampling on the San Juan Islands reveals no evidence for the spread of the Vancouver Island Cryptococcus gattii outbreak to this locale.

Journal Article FEMS Yeast Res · June 2006 Biological diversity has been estimated for various phyla of life, such as insects and mammals, but in the microbe world is has been difficult to determine species richness and abundance. Here we describe a study of species diversity of fungi with a yeast- ... Full text Link to item Cite

Immunotherapy with tacrolimus (FK506) does not select for resistance to calcineurin inhibitors in Candida albicans isolates from liver transplant patients.

Journal Article Antimicrob Agents Chemother · April 2006 In Candida albicans, calcineurin mediates tolerance to azole antifungal drugs, survival in serum, and virulence. In this study, we examined 24 Candida isolates from liver transplant recipients receiving a calcineurin inhibitor as a component of their immun ... Full text Link to item Cite

The Phycomyces madA gene encodes a blue-light photoreceptor for phototropism and other light responses.

Journal Article Proc Natl Acad Sci U S A · March 21, 2006 Phycomyces blakesleeanus is a filamentous zygomycete fungus that produces striking elongated single cells that extend up to 10 cm into the air, with each such sporangiophore supporting a sphere containing the spores for dispersal. This organism has served ... Full text Link to item Cite

Calcineurin, Mpk1 and Hog1 MAPK pathways independently control fludioxonil antifungal sensitivity in Cryptococcus neoformans.

Journal Article Microbiology (Reading) · March 2006 Fludioxonil is employed as an agricultural fungicide to control plant-pathogenic fungi such as Botrytis cinerea. Cryptococcus neoformans is a basidiomycetous human fungal pathogen that causes fatal disease in immunocompromised hosts. This paper demonstrate ... Full text Link to item Cite

G protein-coupled receptor Gpr4 senses amino acids and activates the cAMP-PKA pathway in Cryptococcus neoformans.

Journal Article Mol Biol Cell · February 2006 The Galpha protein Gpa1 governs the cAMP-PKA signaling pathway and plays a central role in virulence and differentiation in the human fungal pathogen Cryptococcus neoformans, but the signals and receptors that trigger this pathway were unknown. We identifi ... Full text Link to item Cite

Recombination hotspots flank the Cryptococcus mating-type locus: implications for the evolution of a fungal sex chromosome.

Journal Article PLoS genetics · 2006 Recombination increases dramatically during meiosis to promote genetic exchange and generate recombinant progeny. Interestingly, meiotic recombination is unevenly distributed throughout genomes, and, as a consequence, genetic and physical map distances do ... Full text Cite

The biology of the Cryptococcus neoformans species complex.

Journal Article Annu Rev Microbiol · 2006 Cryptococcus neoformans is a major cause of fungal meningoencephalitis in immunocompromised patients. Despite recent advances in the genetics and molecular biology of C. neoformans, and improved techniques for molecular epidemiology, aspects of the ecology ... Full text Link to item Cite

Cryptococcus neoformans gene involved in mammalian pathogenesis identified by a Caenorhabditis elegans progeny-based approach.

Journal Article Infect Immun · December 2005 Caenorhabditis elegans can serve as a substitute host for the study of microbial pathogenesis. We found that mutations in genes of the fungal pathogen Cryptococcus neoformans involved in mammalian virulence allow C. elegans to produce greater numbers of pr ... Full text Link to item Cite

Pde1 phosphodiesterase modulates cyclic AMP levels through a protein kinase A-mediated negative feedback loop in Cryptococcus neoformans.

Journal Article Eukaryot Cell · December 2005 The virulence of the human pathogenic fungus Cryptococcus neoformans is regulated by a cyclic AMP (cAMP)-dependent protein kinase A (PKA) signaling cascade that promotes mating and the production of melanin and capsule. In this study, genes encoding homolo ... Full text Link to item Cite

Chromosomal sex-determining regions in animals, plants and fungi.

Journal Article Curr Opin Genet Dev · December 2005 The independent evolution of sex chromosomes in many eukaryotic species raises questions about the evolutionary forces that drive their formation. Recent advances in our understanding of these genomic structures in mammals in parallel with alternate models ... Full text Link to item Cite

Carbonic anhydrase and CO2 sensing during Cryptococcus neoformans growth, differentiation, and virulence.

Journal Article Curr Biol · November 22, 2005 The gas carbon dioxide (CO2) plays a critical role in microbial and mammalian respiration, photosynthesis in algae and plants, chemoreception in insects, and even global warming . However, how CO2 is transported, sensed, and metabolized by microorganisms i ... Full text Link to item Cite

Interaction between genetic background and the mating-type locus in Cryptococcus neoformans virulence potential.

Journal Article Genetics · November 2005 The study of quantitative traits provides a window on the interactions between multiple unlinked genetic loci. The interaction between hosts and pathogenic microbes, such as fungi, involves aspects of quantitative genetics for both partners in this dynamic ... Full text Link to item Cite

Antifungal management practices and evolution of infection in organ transplant recipients with cryptococcus neoformans infection.

Journal Article Transplantation · October 27, 2005 BACKGROUND: Therapeutic practices for Cryptococcus neoformans infection in transplant recipients vary, particularly with regards to antifungal agent employed, and duration of therapy. The risk of relapse and time to recurrence is not known. We assessed ant ... Full text Link to item Cite

Same-sex mating and the origin of the Vancouver Island Cryptococcus gattii outbreak.

Journal Article Nature · October 27, 2005 Genealogy can illuminate the evolutionary path of important human pathogens. In some microbes, strict clonal reproduction predominates, as with the worldwide dissemination of Mycobacterium leprae, the cause of leprosy. In other pathogens, sexual reproducti ... Full text Link to item Cite

Photosensing fungi: phytochrome in the spotlight.

Journal Article Curr Biol · October 25, 2005 Red light triggers asexual development and represses sexual development in the fungus Aspergillus nidulans. This response has been shown to require a phytochrome red/far-red light photoreceptor, FphA, which is cytoplasmic and binds a tetrapyrrole chromopho ... Full text Link to item Cite

Deciphering the model pathogenic fungus Cryptococcus neoformans.

Journal Article Nat Rev Microbiol · October 2005 Cryptococcus neoformans is a basidiomycete fungal pathogen of humans that has diverged considerably from other model fungi such as Neurospora crassa, Aspergillus nidulans, Saccharomyces cerevisiae and the common human fungal pathogen Candida albicans. The ... Full text Link to item Cite

Chlamydospore formation during hyphal growth in Cryptococcus neoformans.

Journal Article Eukaryot Cell · October 2005 Cryptococcus neoformans, a basidiomycetous fungal pathogen, infects hosts through inhalation and can cause fatal meningoencephalitis in individuals if untreated. This fungus undergoes a dimorphic transition from yeast to filamentous growth during mating an ... Full text Link to item Cite

Galpha subunit Gpa2 recruits kelch repeat subunits that inhibit receptor-G protein coupling during cAMP-induced dimorphic transitions in Saccharomyces cerevisiae.

Journal Article Mol Biol Cell · October 2005 All eukaryotic cells sense extracellular stimuli and activate intracellular signaling cascades via G protein-coupled receptors (GPCR) and associated heterotrimeric G proteins. The Saccharomyces cerevisiae GPCR Gpr1 and associated Galpha subunit Gpa2 sense ... Full text Link to item Cite

Cell biology. A fungal Achilles' heel.

Journal Article Science · September 30, 2005 Full text Link to item Cite

Isolation of Cryptococcus gattii and Cryptococcus neoformans var. grubii from the flowers and bark of Eucalyptus trees in India.

Journal Article Med Mycol · September 2005 The association of Cryptococcus gattii with Eucalyptus trees has been well established. Here we report the isolation of both C. gattii and Cryptococcus neoformans var. grubii from the flowers and bark of Eucalyptus trees in India. We investigated a total o ... Full text Link to item Cite

Calcineurin-binding protein Cbp1 directs the specificity of calcineurin-dependent hyphal elongation during mating in Cryptococcus neoformans.

Journal Article Eukaryot Cell · September 2005 Mating and virulence of the human fungal pathogen Cryptococcus neoformans are controlled by calcineurin, a serine-threonine-specific calcium-activated phosphatase that is the target of the immunosuppressive drugs cyclosporine A and FK506. In previous studi ... Full text Link to item Cite

Calcineurin is required for Candida albicans to survive calcium stress in serum.

Journal Article Infect Immun · September 2005 The calcium-activated protein phosphatase calcineurin plays a critical role in the virulence of Candida albicans. Previous studies demonstrated that calcineurin is not required for the yeast-hypha dimorphic transition, host cell adherence, or host cell inj ... Full text Link to item Cite

Novel gene functions required for melanization of the human pathogen Cryptococcus neoformans.

Journal Article Mol Microbiol · September 2005 The ability to produce melanin is a key virulence factor in many fungal pathogens including the human basidiomycete pathogen Cryptococcus neoformans, a major cause of life-threatening infections among immunocompromised persons. Despite the significance of ... Full text Link to item Cite

Cryptococcus neoformans {alpha} strains preferentially disseminate to the central nervous system during coinfection.

Journal Article Infect Immun · August 2005 Cryptococcus neoformans is a fungal pathogen that has evolved over the past 40 million years into three distinct varieties or sibling species (gattii, grubii, and neoformans). Each variety manifests differences in epidemiology and disease, and var. grubii ... Full text Link to item Cite

Clinical and environmental isolates of Cryptococcus gattii from Australia that retain sexual fecundity.

Journal Article Eukaryot Cell · August 2005 Cryptococcus gattii is a primary pathogenic yeast that causes disease in both animals and humans. It is closely related to Cryptococcus neoformans and diverged from a common ancestor approximately 40 million years ago. While C. gattii has a characterized s ... Full text Link to item Cite

Clonality and recombination in genetically differentiated subgroups of Cryptococcus gattii.

Journal Article Eukaryot Cell · August 2005 Cryptococcus gattii is a pathogenic yeast that together with Cryptococcus neoformans causes cryptococcosis in humans and animals. High numbers of viable C. gattii propagules can be obtained from certain species of Australian Eucalyptus camaldulensis trees, ... Full text Link to item Cite

Cryptococcus neoformans gene expression during murine macrophage infection.

Journal Article Eukaryot Cell · August 2005 The fungal pathogen Cryptococcus neoformans survives phagocytosis by macrophages and proliferates within, ultimately establishing latent infection as a facultative intracellular pathogen that can escape macrophage control to cause disseminated disease. Thi ... Full text Link to item Cite

Cyclophilin B escorts the hepatitis C virus RNA polymerase: a viral achilles heel?

Journal Article Mol Cell · July 22, 2005 A recent report by Watashi et al. (2005) in Molecular Cell reveals a role for the host cell prolyl isomerase cyclophilin B (CyPB) in the replication of the hepatitis C viral genome, opening potential avenues for antiviral therapeutic intervention. ... Full text Link to item Cite

Galleria mellonella as a model system to study Cryptococcus neoformans pathogenesis.

Journal Article Infect Immun · July 2005 Evaluation of Cryptococcus neoformans virulence in a number of nonmammalian hosts suggests that C. neoformans is a nonspecific pathogen. We used the killing of Galleria mellonella (the greater wax moth) caterpillar by C. neoformans to develop an invertebra ... Full text Link to item Cite

Calcium- and calcineurin-independent roles for calmodulin in Cryptococcus neoformans morphogenesis and high-temperature growth.

Journal Article Eukaryot Cell · June 2005 The function of calcium as a signaling molecule is conserved in eukaryotes from fungi to humans. Previous studies have identified the calcium-activated phosphatase calcineurin as a critical factor in governing growth of the human pathogenic fungus Cryptoco ... Full text Link to item Cite

Specialization of the HOG pathway and its impact on differentiation and virulence of Cryptococcus neoformans.

Journal Article Mol Biol Cell · May 2005 The human pathogenic fungus Cryptococcus neoformans has diverged from a common ancestor into three biologically distinct varieties or sibling species over the past 10-40 million years. During evolution of these divergent forms, serotype A C. neoformans var ... Full text Link to item Cite

Sexual reproduction between partners of the same mating type in Cryptococcus neoformans.

Journal Article Nature · April 21, 2005 Cryptococcus neoformans is a globally distributed human fungal pathogen that causes life-threatening meningoencephalitis in immunocompromised patients. It has a defined sexual cycle involving haploid cells of alpha and a mating types, yet the vast majority ... Full text Link to item Cite

Light controls growth and development via a conserved pathway in the fungal kingdom.

Journal Article PLoS Biol · April 2005 Light inhibits mating and haploid fruiting of the human fungal pathogen Cryptococcus neoformans, but the mechanisms involved were unknown. Two genes controlling light responses were discovered through candidate gene and insertional mutagenesis approaches. ... Full text Link to item Cite

Sex-specific homeodomain proteins Sxi1alpha and Sxi2a coordinately regulate sexual development in Cryptococcus neoformans.

Journal Article Eukaryot Cell · March 2005 Homeodomain proteins are central regulators of development in eukaryotes. In fungi, homeodomain proteins have been shown to control cell identity and sexual development. Cryptococcus neoformans is a human fungal pathogen with a defined sexual cycle that pr ... Full text Link to item Cite

The genome of the basidiomycetous yeast and human pathogen Cryptococcus neoformans.

Journal Article Science · February 25, 2005 Cryptococcus neoformans is a basidiomycetous yeast ubiquitous in the environment, a model for fungal pathogenesis, and an opportunistic human pathogen of global importance. We have sequenced its approximately 20-megabase genome, which contains approximatel ... Full text Link to item Cite

Chromosomal translocation and segmental duplication in Cryptococcus neoformans.

Journal Article Eukaryot Cell · February 2005 Large chromosomal events such as translocations and segmental duplications enable rapid adaptation to new environments. Here we marshal genomic, genetic, meiotic mapping, and physical evidence to demonstrate that a chromosomal translocation and segmental d ... Full text Link to item Cite

Transcriptional network of multiple capsule and melanin genes governed by the Cryptococcus neoformans cyclic AMP cascade.

Journal Article Eukaryot Cell · January 2005 Cryptococcus neoformans is an opportunistic human fungal pathogen that elaborates several virulence attributes, including a polysaccharide capsule and melanin pigments. A conserved Galpha protein/cyclic AMP (cAMP) pathway controls melanin and capsule produ ... Full text Link to item Cite

Cryptococcus neoformans isolates from transplant recipients are not selected for resistance to calcineurin inhibitors by current immunosuppressive regimens.

Journal Article J Clin Microbiol · January 2005 The immunosuppressants tacrolimus (FK506) and cyclosporine A inhibit calcineurin and have potent antifungal activity. In this study, 24% of Cryptococcus neoformans isolates from solid-organ transplant patients exhibited altered sensitivity to these drugs, ... Full text Link to item Cite

Light controls growth and development via a conserved pathway in the fungal kingdom

Journal Article PLoS Biology · 2005 Light inhibits mating and haploid fruiting of the human fungal pathogen Cryptococcus neoformans, but the mechanisms involved were unknown. Two genes controlling light responses were discovered through candidate gene and insertional mutagenesis approaches. ... Full text Cite

The cyclophilins.

Journal Article Genome Biol · 2005 Cyclophilins (Enzyme Commission (EC) number 5.1.2.8) belong to a group of proteins that have peptidyl-prolyl cis-trans isomerase activity; such proteins are collectively known as immunophilins and also include the FK-506-binding proteins and the parvulins. ... Full text Link to item Cite

Cyclophilin A is localized to the nucleus and controls meiosis in Saccharomyces cerevisiae.

Journal Article Eukaryot Cell · January 2005 Cyclophilin A is conserved from yeast to humans and mediates the ability of cyclosporine to perturb signal transduction cascades via inhibition of calcineurin. Cyclophilin A also catalyzes cis-trans peptidyl-prolyl isomerization during protein folding or c ... Full text Link to item Cite

In vitro interactions between antifungals and immunosuppressants against Aspergillus fumigatus isolates from transplant and nontransplant patients.

Journal Article Antimicrob Agents Chemother · December 2004 We performed in vitro antifungal checkerboard testing on 12 Aspergillus fumigatus clinical isolates (6 transplant recipients and 6 nontransplant patients) with three antifungal agents (amphotericin B, voriconazole, and caspofungin) and three immunosuppress ... Full text Link to item Cite

Adenylyl cyclase-associated protein Aca1 regulates virulence and differentiation of Cryptococcus neoformans via the cyclic AMP-protein kinase A cascade.

Journal Article Eukaryot Cell · December 2004 The evolutionarily conserved cyclic AMP (cAMP) signaling pathway controls cell functions in response to environmental cues in organisms as diverse as yeast and mammals. In the basidiomycetous human pathogenic fungus Cryptococcus neoformans, the cAMP pathwa ... Full text Link to item Cite

Convergent evolution of chromosomal sex-determining regions in the animal and fungal kingdoms.

Journal Article PLoS Biol · December 2004 Sexual identity is governed by sex chromosomes in plants and animals, and by mating type (MAT) loci in fungi. Comparative analysis of the MAT locus from a species cluster of the human fungal pathogen Cryptococcus revealed sequential evolutionary events tha ... Full text Link to item Cite

The calcineurin target, Crz1, functions in azole tolerance but is not required for virulence of Candida albicans.

Journal Article Infect Immun · December 2004 In Candida albicans, calcineurin is essential for virulence and survival during membrane perturbation by azoles. Crz1 is a proposed downstream target of calcineurin based on studies of Saccharomyces cerevisiae. However, the in vitro phenotypes of C. albica ... Full text Link to item Cite

A Sch9 protein kinase homologue controlling virulence independently of the cAMP pathway in Cryptococcus neoformans.

Journal Article Curr Genet · November 2004 The polysaccharide capsule is one of the established virulence factors in Cryptococcus neoformans that provides a barrier against the host-mediated immune response. Mutation of the gene encoding the Saccharomyces cerevisiae Sch9 protein kinase homologue re ... Full text Link to item Cite

Identification of Cryptococcus neoformans temperature-regulated genes with a genomic-DNA microarray.

Journal Article Eukaryot Cell · October 2004 The ability to survive and proliferate at 37 degrees C is an essential virulence attribute of pathogenic microorganisms. A partial-genome microarray was used to profile gene expression in the human-pathogenic fungus Cryptococcus neoformans during growth at ... Full text Link to item Cite

Cryptococcus neoformans mitochondrial genomes from serotype A and D strains do not influence virulence.

Journal Article Curr Genet · October 2004 Cryptococcus neoformans is an encapsulated pathogenic yeast producing meningoencephalitis. Two primary strains in genetic studies, serotype A H99 and serotype D JEC21, possess dramatic differences in virulence. Since it has been shown that mitochondrial ge ... Full text Link to item Cite

FKBP12 controls aspartate pathway flux in Saccharomyces cerevisiae to prevent toxic intermediate accumulation.

Journal Article Eukaryot Cell · October 2004 FKBP12 is a conserved member of the prolyl-isomerase enzyme family and serves as the intracellular receptor for FK506 that mediates immunosuppression in mammals and antimicrobial actions in fungi. To investigate the cellular functions of FKBP12 in Saccharo ... Full text Link to item Cite

Cryptococcus neoformans Kin1 protein kinase homologue, identified through a Caenorhabditis elegans screen, promotes virulence in mammals.

Journal Article Mol Microbiol · October 2004 Cryptococcal infections are a global cause of significant morbidity and mortality. Recent studies support the hypothesis that virulence of Cryptococcus neoformans may have evolved via survival selection in environmental hosts, such as amoebae and free-livi ... Full text Link to item Cite

PAK kinases Ste20 and Pak1 govern cell polarity at different stages of mating in Cryptococcus neoformans.

Journal Article Mol Biol Cell · October 2004 Sexual identity and mating are linked to virulence of the fungal pathogen Cryptococcus neoformans. Cells of the alpha mating type are more prevalent and can be more virulent than a cells, and basidiospores are thought to be the infectious propagule. Mating ... Full text Link to item Cite

Prolyl isomerases in yeast.

Journal Article Front Biosci · September 1, 2004 Prolyl isomerases are enzymes that catalyze cis-trans isomerization of peptidyl-prolyl bonds and span three structurally unrelated protein families: the cyclophilins, FKBPs, and parvulins. The genome of the budding yeast Saccharomyces cerevisiae encodes ei ... Full text Link to item Cite

Investigation of the basis of virulence in serotype A strains of Cryptococcus neoformans from apparently immunocompetent individuals.

Journal Article Curr Genet · August 2004 Cryptococcus neoformans serotype A strains commonly infect immunocompromised patients to cause fungal meningitis. To understand the basis of serotype A cryptococcal infections in apparently immunocompetent patients, we tested two hypotheses: the strains we ... Full text Link to item Cite

A genetic linkage map of Cryptococcus neoformans variety neoformans serotype D (Filobasidiella neoformans).

Journal Article Genetics · June 2004 To construct a genetic linkage map of the heterothallic yeast, Cryptococcus neoformans (Filobasidiella neoformans), we crossed two mating-compatible strains and analyzed 94 progeny for the segregation of 301 polymorphic markers, consisting of 228 restricti ... Full text Link to item Cite

The alpha-specific cell identity factor Sxi1alpha is not required for virulence of Cryptococcus neoformans.

Journal Article Infect Immun · June 2004 Cryptococcus neoformans is a human fungal pathogen that has two mating types (a and alpha). Experiments have shown that in some backgrounds alpha strains are more virulent than a strains. Our studies reveal that the only known alpha-specific factor, SXI1al ... Full text Link to item Cite

In vitro interactions between antifungals and immunosuppressants against Aspergillus fumigatus.

Journal Article Antimicrob Agents Chemother · May 2004 The optimal treatment for invasive aspergillosis remains elusive, despite the increased efficacy of newer agents. The immunosuppressants cyclosporine (CY), tacrolimus (FK506), and sirolimus (formerly called rapamycin) exhibit in vitro and in vivo activity ... Full text Link to item Cite

Cryptococcus neoformans virulence gene discovery through insertional mutagenesis.

Journal Article Eukaryot Cell · April 2004 Insertional mutagenesis was applied to Cryptococcus neoformans to identify genes associated with virulence attributes. Using biolistic transformation, we generated 4,300 nourseothricin (NAT)-resistant strains, of which 590 exhibited stable resistance. We f ... Full text Link to item Cite

Challenge of Drosophila melanogaster with Cryptococcus neoformans and role of the innate immune response.

Journal Article Eukaryot Cell · April 2004 We found that the ingestion of Cryptococcus neoformans by Drosophila melanogaster resulted in the death of the fly but that the ingestion of Saccharomyces cerevisiae or the nonpathogenic Cryptococcus kuetzingii or Cryptococcus laurentii did not. The C. neo ... Full text Link to item Cite

Calcineurin: a central controller of signalling in eukaryotes.

Journal Article EMBO Rep · April 2004 Workshop on the Calcium/Calcineurin/NFAT Pathway: Regulation and Function ... Full text Link to item Cite

Antifungal attributes of immunosuppressive agents: new paradigms in management and elucidating the pathophysiologic basis of opportunistic mycoses in organ transplant recipients.

Journal Article Transplantation · March 27, 2004 The currently available immunosuppressive agents cyclosporine A, tacrolimus, and rapamycin have potent antifungal activity against a number of opportunistic fungi in organ transplant recipients, most notably, C. neoformans, Candida, and Aspergillus species ... Full text Link to item Cite

Cryptococcus neoformans shows a remarkable genotypic diversity in Brazil.

Journal Article J Clin Microbiol · March 2004 The genotypic diversity of Brazilian Cryptococcus neoformans strains was analyzed. The majority of the samples were alphaA (65%), followed by alphaB (17.5%), alphaD (9%), alphaAaD hybrids (5%), and alphaC (3.5%). A considerable genotypic diversity occurred ... Full text Link to item Cite

Cyclic AMP-dependent protein kinase catalytic subunits have divergent roles in virulence factor production in two varieties of the fungal pathogen Cryptococcus neoformans.

Journal Article Eukaryot Cell · February 2004 Our earlier findings established that cyclic AMP-dependent protein kinase functions in a signaling cascade that regulates mating and virulence of Cryptococcus neoformans var. grubii (serotype A). Mutants lacking the serotype A protein kinase A (PKA) cataly ... Full text Link to item Cite

Evolution of fungal sex chromosomes.

Journal Article Mol Microbiol · January 2004 Sexual reproduction enables organisms to shuffle two parental genomes to produce recombinant progeny, and to purge the genome of deleterious mutations. Sex is conserved in virtually all organisms, from bacteria and fungi to plants and animals, and yet the ... Full text Link to item Cite

Evidence of sexual recombination among Cryptococcus neoformans serotype A isolates in sub-Saharan Africa.

Journal Article Eukaryot Cell · December 2003 The most common cause of fungal meningitis in humans, Cryptococcus neoformans serotype A, is a basidiomycetous yeast with a bipolar mating system. However, the vast majority (>99.9%) of C. neoformans serotype A isolates possess only one of the two mating t ... Full text Link to item Cite

Coping with stress: calmodulin and calcineurin in model and pathogenic fungi.

Journal Article Biochem Biophys Res Commun · November 28, 2003 Calcium signaling via calmodulin and calcineurin is critical for the regulation of stress responses in fungi. The functions of calmodulin and calcineurin are largely conserved among pathogenic fungi and model fungi, however, the mechanisms of action have d ... Full text Link to item Cite

Enzymes that counteract nitrosative stress promote fungal virulence.

Journal Article Curr Biol · November 11, 2003 Enzymes that protect cells from reactive oxygen species (superoxide dismutase, catalase, peroxidase) have well-established roles in mammalian biology and microbial pathogenesis. Two recently identified enzymes detoxify nitric oxide (NO)-related molecules; ... Full text Link to item Cite

Fungal mating-type loci.

Journal Article Curr Biol · October 14, 2003 Full text Link to item Cite

Recapitulation of the sexual cycle of the primary fungal pathogen Cryptococcus neoformans var. gattii: implications for an outbreak on Vancouver Island, Canada.

Journal Article Eukaryot Cell · October 2003 Cryptococcus neoformans is a human fungal pathogen that exists as three distinct varieties or sibling species: the predominantly opportunistic pathogens C. neoformans var. neoformans (serotype D) and C. neoformans var. grubii (serotype A) and the primary p ... Full text Link to item Cite

Phospholipid-binding protein Cts1 controls septation and functions coordinately with calcineurin in Cryptococcus neoformans.

Journal Article Eukaryot Cell · October 2003 Cryptococcus neoformans is an opportunistic fungal pathogen that causes life-threatening meningoencephalitis in immunocompromised patients. The Ca(2+)-calmodulin-activated protein phosphatase calcineurin is necessary for virulence of C. neoformans. Mutants ... Full text Link to item Cite

Disruption of ergosterol biosynthesis confers resistance to amphotericin B in Candida lusitaniae.

Journal Article Antimicrob Agents Chemother · September 2003 Candida lusitaniae is an emerging human pathogen that, unlike other fungal pathogens, frequently develops resistance to the commonly used antifungal agent amphotericin B. Amphotericin B is a member of the polyene class of antifungal drugs, which impair fun ... Full text Link to item Cite

Sexual cycle of Cryptococcus neoformans var. grubii and virulence of congenic a and alpha isolates.

Journal Article Infect Immun · September 2003 Featured Publication Cryptococcus neoformans is a human-pathogenic fungus that has evolved into three distinct varieties that infect most prominently the central nervous system. A sexual cycle involving haploid cells of a and alpha mating types has been reported for two variet ... Full text Link to item Cite

A MAP kinase cascade composed of cell type specific and non-specific elements controls mating and differentiation of the fungal pathogen Cryptococcus neoformans.

Journal Article Mol Microbiol · July 2003 Cryptococcus neoformans is an opportunistic fungal pathogen with a defined sexual cycle in which the alpha allele of the mating type locus is linked to virulence and haploid differentiation. Here we analysed a conserved MAP kinase cascade composed of matin ... Full text Link to item Cite

Calcineurin is essential for Candida albicans survival in serum and virulence.

Journal Article Eukaryot Cell · June 2003 Calcineurin is a calcium-activated protein phosphatase that is the target of the immunosuppressants cyclosporin A and FK506. In T cells, calcineurin controls nuclear import of the NF-AT transcription factor and gene activation. In plants and fungi, calcine ... Full text Link to item Cite

The Cryptococcus neoformans MAP kinase Mpk1 regulates cell integrity in response to antifungal drugs and loss of calcineurin function.

Journal Article Mol Microbiol · June 2003 Cell wall integrity is crucial for fungal growth, development and stress survival. In the model yeast Saccharomyces cerevisiae, the cell integrity Mpk1/Slt2 MAP kinase and calcineurin pathways monitor cell wall integrity and promote cell wall remodelling u ... Full text Link to item Cite

A nomenclature for restriction enzymes, DNA methyltransferases, homing endonucleases and their genes.

Journal Article Nucleic Acids Res · April 1, 2003 A nomenclature is described for restriction endonucleases, DNA methyltransferases, homing endonucleases and related genes and gene products. It provides explicit categories for the many different Type II enzymes now identified and provides a system for nam ... Full text Link to item Cite

Ergosterol biosynthesis inhibitors become fungicidal when combined with calcineurin inhibitors against Candida albicans, Candida glabrata, and Candida krusei.

Journal Article Antimicrob Agents Chemother · March 2003 Azoles target the ergosterol biosynthetic enzyme lanosterol 14alpha-demethylase and are a widely applied class of antifungal agents because of their broad therapeutic window, wide spectrum of activity, and low toxicity. Unfortunately, azoles are generally ... Full text Link to item Cite

Ras1 controls pheromone expression and response during mating in Cryptococcus neoformans.

Journal Article Fungal Genet Biol · February 2003 The Cryptococcus neoformans Ras1 signal transduction pathway controls mating, hyphal differentiation, and the ability of this opportunistic human fungal pathogen to grow at elevated temperatures. To further elucidate how Ras1 signals in this organism, the ... Full text Link to item Cite

Teaching old drugs new tricks: reincarnating immunosuppressants as antifungal drugs.

Journal Article Curr Opin Investig Drugs · February 2003 Invasive fungal infections are rising worldwide as the number of immunocompromised patients increases. Unfortunately, our armamentarium of antifungal drugs is limited. Although current therapies are effective in treating some of the most prevalent infectio ... Link to item Cite

Cell identity and sexual development in Cryptococcus neoformans are controlled by the mating-type-specific homeodomain protein Sxi1alpha.

Journal Article Genes Dev · December 1, 2002 Featured Publication Virulence in the human fungal pathogen Cryptococcus neoformans is associated with the alpha mating type. Studies to identify the properties of alpha cells that enhance pathogenesis have led to the identification of a mating-type locus of unusually large si ... Full text Link to item Cite

Killing of Caenorhabditis elegans by Cryptococcus neoformans as a model of yeast pathogenesis.

Journal Article Proc Natl Acad Sci U S A · November 26, 2002 We found that the well-studied nematode Caenorhabditis elegans can use various yeasts, including Cryptococcus laurentii and Cryptococcus kuetzingii, as a sole source of food, producing similar brood sizes compared with growth on its usual laboratory food s ... Full text Link to item Cite

Fungal mating: Candida albicans flips a switch to get in the mood.

Journal Article Curr Biol · November 19, 2002 The fungal pathogen Candida albicans can mate under highly controlled conditions. It can also undergo phenotypic switching. A recent discovery joins these disparate processes to reveal that 'opaque' switch variants mate 10(6) times better than 'white' vari ... Full text Link to item Cite

Good fungi gone bad: the corruption of calcineurin.

Journal Article Bioessays · October 2002 Calcineurin is a Ca(2+)/calmodulin-activated protein phosphatase that is conserved in eukaryotes, from yeast to humans, and is the conserved target of the immunosuppressive drugs cyclosporin A (CsA) and FK506. Genetic studies in yeast and fungi established ... Full text Link to item Cite

Mating-type locus of Cryptococcus neoformans: a step in the evolution of sex chromosomes.

Journal Article Eukaryot Cell · October 2002 Featured Publication The sexual development and virulence of the fungal pathogen Cryptococcus neoformans is controlled by a bipolar mating system determined by a single locus that exists in two alleles, alpha and a. The alpha and a mating-type alleles from two divergent variet ... Full text Link to item Cite

Physical maps for genome analysis of serotype A and D strains of the fungal pathogen Cryptococcus neoformans.

Journal Article Genome Res · September 2002 The basidiomycete fungus Cryptococcus neoformans is an important opportunistic pathogen of humans that poses a significant threat to immunocompromised individuals. Isolates of C. neoformans are classified into serotypes (A, B, C, D, and AD) based on antige ... Full text Link to item Cite

A PCR-based strategy to generate integrative targeting alleles with large regions of homology.

Journal Article Microbiology (Reading) · August 2002 Cryptococcus neoformans is an opportunistic fungal pathogen with a defined sexual cycle for which genetic and molecular techniques are well developed. The entire genome sequence of one C. neoformans strain is nearing completion. The efficient use of this s ... Full text Link to item Cite

The Galpha protein Gpa2 controls yeast differentiation by interacting with kelch repeat proteins that mimic Gbeta subunits.

Journal Article Mol Cell · July 2002 Featured Publication G protein coupled receptors (GPCR) sense diverse ligands and signal via heterotrimeric G proteins. The Saccharomyces cerevisiae GPCR Gpr1 senses glucose and controls filamentous growth via an unusual Galpha protein, Gpa2, which lacks any known Gbetagamma s ... Full text Link to item Cite

FKBP12 is the only FK506 binding protein mediating T-cell inhibition by the immunosuppressant FK506.

Journal Article Transplantation · June 15, 2002 BACKGROUND: FK506-binding proteins (FKBP) are immunophilins that interact with the immunosuppressive drugs FK506 and rapamycin. Several FKBP family members such as FKBP12, FKBP12.6, and FKBP51 are expressed in T cells. It has been speculated that these FKB ... Full text Link to item Cite

Protein kinase A operates a molecular switch that governs yeast pseudohyphal differentiation.

Journal Article Mol Cell Biol · June 2002 The yeast Saccharomyces cerevisiae undergoes a dimorphic filamentous transition in response to nutrient cues that is affected by both mitogen-activated protein kinase and cyclic AMP-protein kinase A signaling cascades. Here two transcriptional regulators, ... Full text Link to item Cite

Pheromones stimulate mating and differentiation via paracrine and autocrine signaling in Cryptococcus neoformans.

Journal Article Eukaryot Cell · June 2002 Cryptococcus neoformans is a pathogenic fungus with a defined sexual cycle involving haploid MATalpha and MATa cells. Interestingly, MATalpha strains are more common, are more virulent than congenic MATa strains, and undergo haploid fruiting in response to ... Full text Link to item Cite

Mating-type-specific and nonspecific PAK kinases play shared and divergent roles in Cryptococcus neoformans.

Journal Article Eukaryot Cell · April 2002 Cryptococcus neoformans is an opportunistic fungal pathogen with a defined sexual cycle involving fusion of haploid MATalpha and MATa cells. Virulence has been linked to the mating type, and MATalpha cells are more virulent than congenic MATa cells. To stu ... Full text Link to item Cite

Yeasts as Model-T cells

Journal Article FASEB JOURNAL · March 22, 2002 Link to item Cite

Calcineurin is essential for survival during membrane stress in Candida albicans.

Journal Article EMBO J · February 15, 2002 Featured Publication The immunosuppressants cyclosporin A (CsA) and FK506 inhibit the protein phosphatase calcineurin and block T-cell activation and transplant rejection. Calcineurin is conserved in microorganisms and plays a general role in stress survival. CsA and FK506 are ... Full text Link to item Cite

Adenylyl cyclase functions downstream of the Galpha protein Gpa1 and controls mating and pathogenicity of Cryptococcus neoformans.

Journal Article Eukaryot Cell · February 2002 The signaling molecule cyclic AMP (cAMP) is a ubiquitous second messenger that enables cells to detect and respond to extracellular signals. cAMP is generated by the enzyme adenylyl cyclase, which is activated or inhibited by the Galpha subunits of heterot ... Full text Link to item Cite

Genetics of Cryptococcus neoformans.

Journal Article Annu Rev Genet · 2002 Featured Publication Cryptococcus neoformans is a pathogenic fungus that primarily afflicts immunocompromised patients, infecting the central nervous system to cause meningoencephalitis that is uniformly fatal if untreated. C. neoformans is a basidiomycetous fungus with a defi ... Full text Link to item Cite

Ras1 and Ras2 contribute shared and unique roles in physiology and virulence of Cryptococcus neoformans.

Journal Article Microbiology (Reading) · January 2002 The Ras1 signal transduction pathway controls the ability of the pathogenic fungus Cryptococcus neoformans to grow at high temperatures and to mate. A second RAS gene was identified in this organism. RAS2 is expressed at a very low level compared to RAS1, ... Full text Link to item Cite

Ras1 and Ras2 contribute shared and unique roles in physiology and virulence of Cryptococcus neoformans

Journal Article Microbiology · 2002 The Ras1 signal transduction pathway controls the ability of the pathogenic fungus Cryptococcus neoformans to grow at high temperatures and to mate. A second RAS gene was identified in this organism. RAS2 is expressed at a very low level compared to RAS1, ... Cite

The TOR signal transduction cascade controls cellular differentiation in response to nutrients.

Journal Article Mol Biol Cell · December 2001 Rapamycin binds and inhibits the Tor protein kinases, which function in a nutrient-sensing signal transduction pathway that has been conserved from the yeast Saccharomyces cerevisiae to humans. In yeast cells, the Tor pathway has been implicated in regulat ... Full text Link to item Cite

Rapamycin and less immunosuppressive analogs are toxic to Candida albicans and Cryptococcus neoformans via FKBP12-dependent inhibition of TOR.

Journal Article Antimicrob Agents Chemother · November 2001 Candida albicans and Cryptococcus neoformans cause both superficial and disseminated infections in humans. Current antifungal therapies for deep-seated infections are limited to amphotericin B, flucytosine, and azoles. A limitation is that commonly used az ... Full text Link to item Cite

Phytosphingosine as a specific inhibitor of growth and nutrient import in Saccharomyces cerevisiae.

Journal Article J Biol Chem · September 21, 2001 In the yeast Saccharomyces cerevisiae, we have demonstrated a necessary role for sphingolipids in the heat stress response through inhibition of nutrient import (Chung, N., Jenkins, G. M., Hannun, Y. A., Heitman, J., and Obeid, L. M. (2000) J. Biol. Chem. ... Full text Link to item Cite

Two cyclophilin A homologs with shared and distinct functions important for growth and virulence of Cryptococcus neoformans.

Journal Article EMBO Rep · June 2001 Cyclophilin A is the target of the immunosuppressant cyclosporin A (CsA) and is encoded by a single unique gene conserved from yeast to humans. In the pathogenic fungus Cryptococcus neoformans, two homologous linked genes, CPA1 and CPA2, were found to enco ... Full text Link to item Cite

Conserved cAMP signaling cascades regulate fungal development and virulence.

Journal Article FEMS Microbiol Rev · May 2001 Two well characterized signal transduction cascades regulating fungal development and virulence are the MAP kinase and cAMP signaling cascades. Here we review the current state of knowledge on cAMP signaling cascades in fungi. While the processes regulated ... Full text Link to item Cite

Cyclic AMP-dependent protein kinase controls virulence of the fungal pathogen Cryptococcus neoformans.

Journal Article Mol Cell Biol · May 2001 Cryptococcus neoformans is an opportunistic fungal pathogen that infects the human central nervous system. This pathogen elaborates two specialized virulence factors: the antioxidant melanin and an antiphagocytic immunosuppressive polysaccharide capsule. A ... Full text Link to item Cite

The TOR kinases link nutrient sensing to cell growth.

Journal Article J Biol Chem · March 30, 2001 Rapamycin is an immunosuppressive natural product that inhibits the proliferation of T-cells in response to nutrients and growth factors. Rapamycin binds to the peptidyl-prolyl isomerase FKBP12 and forms protein-drug complexes that inhibit signal transduct ... Full text Link to item Cite

A metabolic enzyme for S-nitrosothiol conserved from bacteria to humans.

Journal Article Nature · March 22, 2001 Considerable evidence indicates that NO biology involves a family of NO-related molecules and that S-nitrosothiols (SNOs) are central to signal transduction and host defence. It is unknown, however, how cells switch off the signals or protect themselves fr ... Full text Link to item Cite

Dismantling the Cryptococcus coat

Journal Article Trends in Microbiology · March 2001 Full text Cite

Calcineurin is required for hyphal elongation during mating and haploid fruiting in Cryptococcus neoformans.

Journal Article EMBO J · March 1, 2001 Cryptococcus neoformans is a fungal pathogen that causes meningitis in immunocompromised patients. Its growth is sensitive to the immunosuppressants FK506 and cyclosporin, which inhibit the Ca2+- calmodulin-activated protein phosphatase calcineurin. Calcin ... Full text Link to item Cite

Dismantling the Cryptococcus coat.

Journal Article Trends Microbiol · March 2001 Full text Link to item Cite

Calcineurin regulatory subunit is essential for virulence and mediates interactions with FKBP12-FK506 in Cryptococcus neoformans.

Journal Article Mol Microbiol · February 2001 Calcineurin is a Ca2+-calmodulin-regulated protein phosphatase that is the target of the immunosuppressive drugs cyclosporin A and FK506. Calcineurin is a heterodimer composed of a catalytic A and a regulatory B subunit. In previous studies, the calcineuri ... Full text Link to item Cite

Serotype AD strains of Cryptococcus neoformans are diploid or aneuploid and are heterozygous at the mating-type locus.

Journal Article Infect Immun · January 2001 Cryptococcus neoformans is a pathogenic basidiomycete with a defined sexual cycle involving mating between haploid yeast cells with a transient diploid state. C. neoformans occurs in four predominant serotypes (A, B, C, and D), which represent different va ... Full text Link to item Cite

Identification of the MATa mating-type locus of Cryptococcus neoformans reveals a serotype A MATa strain thought to have been extinct.

Journal Article Proc Natl Acad Sci U S A · December 19, 2000 Cryptococcus neoformans is an opportunistic fungal pathogen with a defined sexual cycle involving mating between haploid MATa and MATalpha cells. Here we describe the isolation of part of the MATa mating-type locus encoding a Ste20 kinase homolog, Ste20a. ... Full text Link to item Cite

Characterization of the MFalpha pheromone of the human fungal pathogen cryptococcus neoformans.

Journal Article Mol Microbiol · December 2000 Cryptococcus neoformans is an important human pathogenic fungus with a defined sexual cycle and well-developed molecular and genetic approaches. C. neoformans is predominantly haploid and has two mating types, MATa and MATalpha. Mating is known to be regul ... Full text Link to item Cite

Signal transduction cascades regulating fungal development and virulence.

Journal Article Microbiol Mol Biol Rev · December 2000 Cellular differentiation, mating, and filamentous growth are regulated in many fungi by environmental and nutritional signals. For example, in response to nitrogen limitation, diploid cells of the yeast Saccharomyces cerevisiae undergo a dimorphic transiti ... Full text Link to item Cite

Signal transduction cascades regulating pseudohyphal differentiation of Saccharomyces cerevisiae.

Journal Article Curr Opin Microbiol · December 2000 In response to nitrogen limitation, diploid cells of the yeast Saccharomyces cerevisiae undergo a dimorphic transition to filamentous pseudohyphal growth. At least two signaling pathways regulate filamentation. One involves components of the MAP kinase cas ... Full text Link to item Cite

Sok2 regulates yeast pseudohyphal differentiation via a transcription factor cascade that regulates cell-cell adhesion.

Journal Article Mol Cell Biol · November 2000 In response to nitrogen limitation, Saccharomyces cerevisiae undergoes a dimorphic transition to filamentous pseudohyphal growth. In previous studies, the transcription factor Sok2 was found to negatively regulate pseudohyphal differentiation. By genome ar ... Full text Link to item Cite

A new face of the Rhesus antigen.

Journal Article Nat Genet · November 2000 Full text Link to item Cite

Identification and characterization of a highly conserved calcineurin binding protein, CBP1/calcipressin, in Cryptococcus neoformans.

Journal Article EMBO J · July 17, 2000 Calcineurin is the conserved target of the immunosuppressants cyclosporin A and FK506. Using the yeast two-hybrid system, we identified a novel calcineurin binding protein, CBP1, from the pathogenic fungus Cryptococcus neoformans. We show that CBP1 binds t ... Full text Link to item Cite

The Ess1 prolyl isomerase is linked to chromatin remodeling complexes and the general transcription machinery.

Journal Article EMBO J · July 17, 2000 The Ess1/Pin1 peptidyl-prolyl isomerase (PPIase) is thought to control mitosis by binding to cell cycle regulatory proteins and altering their activity. Here we isolate temperature-sensitive ess1 mutants and identify six multicopy suppressors that rescue t ... Full text Link to item Cite

Cyclophilin A and Ess1 interact with and regulate silencing by the Sin3-Rpd3 histone deacetylase.

Journal Article EMBO J · July 17, 2000 Three families of prolyl isomerases have been identified: cyclophilins, FK506-binding proteins (FKBPs) and parvulins. All 12 cyclophilins and FKBPs are dispensable for growth in yeast, whereas the one parvulin homolog, Ess1, is essential. We report here th ... Full text Link to item Cite

Sphingolipids signal heat stress-induced ubiquitin-dependent proteolysis.

Journal Article J Biol Chem · June 9, 2000 Sphingolipids are essential eukaryotic membrane lipids that are structurally and metabolically conserved through evolution. Sphingolipids have also been proposed to regulate eukaryotic stress responses as novel second messengers. Here we show that, in Sacc ... Full text Link to item Cite

A STE12 homolog is required for mating but dispensable for filamentation in candida lusitaniae.

Journal Article Genetics · May 2000 Candida lusitaniae is a dimorphic yeast that is emerging as an opportunistic fungal pathogen. In contrast to Candida albicans, which is diploid and asexual, C. lusitaniae has been reported to have a sexual cycle. We have employed genetic approaches to demo ... Full text Link to item Cite

Protection from nitrosative stress by yeast flavohemoglobin.

Journal Article Proc Natl Acad Sci U S A · April 25, 2000 Yeast hemoglobin was discovered close to half a century ago, but its function has remained unknown. Herein, we report that this flavohemoglobin protects Saccharomyces cerevisiae from nitrosative stress. Deletion of the flavohemoglobin gene (YHB1) abolished ... Full text Link to item Cite

Diploid strains of the pathogenic basidiomycete Cryptococcus neoformans are thermally dimorphic.

Journal Article Fungal Genet Biol · April 2000 Cryptococcus neoformans is an opportunistic human pathogenic fungus with a defined sexual cycle. Clinical and environmental isolates of C. neoformans are haploid, and the diploid stage of the lifecycle is thought to be transient and unstable. In contrast, ... Full text Link to item Cite

RAS1 regulates filamentation, mating and growth at high temperature of Cryptococcus neoformans.

Journal Article Mol Microbiol · April 2000 Cryptococcus neoformans is a basidiomycete yeast and opportunistic human pathogen of increasing clinical importance due to the increasing population of immunocompromised patients. To further investigate signal transduction cascades regulating fungal pathog ... Full text Link to item Cite

Synergistic antifungal activities of bafilomycin A(1), fluconazole, and the pneumocandin MK-0991/caspofungin acetate (L-743,873) with calcineurin inhibitors FK506 and L-685,818 against Cryptococcus neoformans.

Journal Article Antimicrob Agents Chemother · March 2000 Cryptococcus neoformans is an opportunistic fungal pathogen that causes life-threatening infections of the central nervous system. Existing therapies include amphotericin B, fluconazole, and flucytosine, which are limited by toxic side effects and the emer ... Full text Link to item Cite

Comparison of the roles of calcineurin in physiology and virulence in serotype D and serotype A strains of Cryptococcus neoformans.

Journal Article Infect Immun · February 2000 The calcineurin gene was cloned and disrupted in serotype D strains of Cryptococcus neoformans. Serotype A and serotype D calcineurin mutants were inviable at 37 degrees C and avirulent in mice, whereas only serotype A mutants were cation stress sensitive. ... Full text Link to item Cite

The G protein-coupled receptor gpr1 is a nutrient sensor that regulates pseudohyphal differentiation in Saccharomyces cerevisiae.

Journal Article Genetics · February 2000 Pseudohyphal differentiation in the budding yeast Saccharomyces cerevisiae is induced in diploid cells in response to nitrogen starvation and abundant fermentable carbon source. Filamentous growth requires at least two signaling pathways: the pheromone res ... Full text Link to item Cite

Gene disruption by biolistic transformation in serotype D strains of Cryptococcus neoformans.

Journal Article Fungal Genet Biol · February 2000 Gene disruption by biolistic transformation in serotype D strains of Cryptococcus neoformans. Fungal Genetics and Biology 29, 38-48. Cryptococcus neoformans is an opportunistic fungal pathogen with a defined sexual cycle and well-developed genetic and mole ... Full text Link to item Cite

Immunosuppressive and nonimmunosuppressive cyclosporine analogs are toxic to the opportunistic fungal pathogen Cryptococcus neoformans via cyclophilin-dependent inhibition of calcineurin.

Journal Article Antimicrob Agents Chemother · January 2000 Cyclosporine (CsA) is an immunosuppressive and antimicrobial drug which, in complex with cyclophilin A, inhibits the protein phosphatase calcineurin. We recently found that Cryptococcus neoformans growth is resistant to CsA at 24 degrees C but sensitive at ... Full text Link to item Cite

The G-protein beta subunit GPB1 is required for mating and haploid fruiting in Cryptococcus neoformans.

Journal Article Mol Cell Biol · January 2000 Cryptococcus neoformans is an opportunistic fungal pathogen with a defined sexual cycle. The gene encoding a heterotrimeric G-protein beta subunit, GPB1, was cloned and disrupted. gpb1 mutant strains are sterile, indicating a role for this gene in mating. ... Full text Link to item Cite

Characterization of alcohol-induced filamentous growth in Saccharomyces cerevisiae.

Journal Article Mol Biol Cell · January 2000 Diploid cells of the budding yeast Saccharomyces cerevisiae starved for nitrogen differentiate into a filamentous growth form. Poor carbon sources such as starches can also stimulate filamentation, whereas haploid cells undergo a similar invasive growth re ... Full text Link to item Cite

Morphogenesis of Cryptococcus neoformans.

Journal Article Contrib Microbiol · 2000 Full text Link to item Cite

The TOR signaling cascade regulates gene expression in response to nutrients.

Journal Article Genes Dev · December 15, 1999 Rapamycin inhibits the TOR kinases, which regulate cell proliferation and mRNA translation and are conserved from yeast to man. The TOR kinases also regulate responses to nutrients, including sporulation, autophagy, mating, and ribosome biogenesis. We have ... Full text Link to item Cite

Comparison of in vitro activities of camptothecin and nitidine derivatives against fungal and cancer cells.

Journal Article Antimicrob Agents Chemother · December 1999 The activities of a series of camptothecin and nitidine derivatives that might interact with topoisomerase I were compared against yeast and cancer cell lines. Our findings reveal that structural modifications to camptothecin derivatives have profound effe ... Full text Link to item Cite

The STE12alpha homolog is required for haploid filamentation but largely dispensable for mating and virulence in Cryptococcus neoformans.

Journal Article Genetics · December 1999 Cryptococcus neoformans is a fungal pathogen that causes meningitis in immunocompromised hosts. The organism has a known sexual cycle, and strains of the MATalpha mating type are more virulent than isogenic MATa strains in mice, and they are more common in ... Full text Link to item Cite

Antifungal activities of antineoplastic agents: Saccharomyces cerevisiae as a model system to study drug action.

Journal Article Clin Microbiol Rev · October 1999 Recent evolutionary studies reveal that microorganisms including yeasts and fungi are more closely related to mammals than was previously appreciated. Possibly as a consequence, many natural-product toxins that have antimicrobial activity are also toxic to ... Full text Link to item Cite

On the origins of congenic MATalpha and MATa strains of the pathogenic yeast Cryptococcus neoformans.

Journal Article Fungal Genet Biol · October 1999 The basidiomycetous yeast Cryptococcus neoformans infects humans and causes a meningoencephalitis that is uniformly fatal if untreated. The organism has a defined sexual cycle involving mating of haploid MATa and MATalpha strains, gene disruption by transf ... Full text Link to item Cite

TOR kinase homologs function in a signal transduction pathway that is conserved from yeast to mammals.

Journal Article Mol Cell Endocrinol · September 10, 1999 Rapamycin is a natural product with potent antifungal and immunosuppressive activities. Rapamycin binds to the FKBP12 prolyl isomerase, and the resulting protein-drug complex inhibits the TOR kinase homologs. Both the FKBP12 and the TOR proteins are highly ... Full text Link to item Cite

DNA nicks inflicted by restriction endonucleases are repaired by a RecA- and RecB-dependent pathway in Escherichia coli.

Journal Article Mol Microbiol · September 1999 Two mutants of the EcoRI endonuclease (R200K and E144C) predominantly nick only one strand of the DNA substrate. Temperature sensitivity of the mutant enzymes allowed us to study the consequences of inflicting DNA nicks at EcoRI sites in vivo. Expression o ... Full text Link to item Cite

Signal transduction cascades regulating mating, filamentation, and virulence in Cryptococcus neoformans.

Journal Article Curr Opin Microbiol · August 1999 Cryptococcus neoformans is a basidiomycetous fungal pathogen that infects the central nervous system. The organism has a defined sexual cycle involving mating between haploid MATalpha and MATa cells. Recent studies have revealed signaling cascades that coo ... Full text Link to item Cite

Secretion of FK506/FK520 and rapamycin by Streptomyces inhibits the growth of competing Saccharomyces cerevisiae and Cryptococcus neoformans.

Journal Article Microbiology (Reading) · August 1999 FK506 and rapamycin are immunosuppressants that inhibit signalling cascades required for T-cell activation, yet both are natural products of Streptomyces that live in the soil. FK506 and rapamycin also have potent antimicrobial activity against yeast and p ... Full text Link to item Cite

Protein kinase activity and identification of a toxic effector domain of the target of rapamycin TOR proteins in yeast.

Journal Article Mol Biol Cell · August 1999 In complex with FKBP12, the immunosuppressant rapamycin binds to and inhibits the yeast TOR1 and TOR2 proteins and the mammalian homologue mTOR/FRAP/RAFT1. The TOR proteins promote cell cycle progression in yeast and human cells by regulating translation a ... Full text Link to item Cite

Cyclic AMP-dependent protein kinase regulates pseudohyphal differentiation in Saccharomyces cerevisiae.

Journal Article Mol Cell Biol · July 1999 In response to nitrogen starvation, diploid cells of the yeast Saccharomyces cerevisiae differentiate to a filamentous growth form known as pseudohyphal differentiation. Filamentous growth is regulated by elements of the pheromone mitogen-activated protein ... Full text Link to item Cite

Rapamycin antifungal action is mediated via conserved complexes with FKBP12 and TOR kinase homologs in Cryptococcus neoformans.

Journal Article Mol Cell Biol · June 1999 Cryptococcus neoformans is a fungal pathogen that causes meningitis in patients immunocompromised by AIDS, chemotherapy, organ transplantation, or high-dose steroids. Current antifungal drug therapies are limited and suffer from toxic side effects and drug ... Full text Link to item Cite

Molecular analysis of the Cryptococcus neoformans ADE2 gene, a selectable marker for transformation and gene disruption.

Journal Article Fungal Genet Biol · June 1999 Cryptococcus neoformans is an important fungal pathogen of man. The incidence of cryptococcal disease has increased dramatically in patients immunocompromised because of HIV infection, organ transplantation, or treatment with cytotoxic chemotherapy or cort ... Full text Link to item Cite

Molecular cloning and characterization of Aspergillus nidulans cyclophilin B.

Journal Article Fungal Genet Biol · June 1999 Cyclophilins are an evolutionarily conserved family of proteins which serve as the intracellular receptors for the immunosuppressive drug cyclosporin A. Here we report the characterization of the first cyclophilin cloned from the filamentous fungus Aspergi ... Full text Link to item Cite

Topoisomerase I is essential in Cryptococcus neoformans: role In pathobiology and as an antifungal target.

Journal Article Genetics · May 1999 Topisomerase I is the target of several toxins and chemotherapy agents, and the enzyme is essential for viability in some organisms, including mice and drosophila. We have cloned the TOP1 gene encoding topoisomerase I from the opportunistic fungal pathogen ... Full text Link to item Cite

Cryptococcus neoformans differential gene expression detected in vitro and in vivo with green fluorescent protein.

Journal Article Infect Immun · April 1999 Synthetic green fluorescent protein (GFP) was used as a reporter to detect differential gene expression in the pathogenic fungus Cryptococcus neoformans. Promoters from the C. neoformans actin, GAL7, or mating-type alpha pheromone (MFalpha1) genes were fus ... Full text Link to item Cite

Hmo1p, a high mobility group 1/2 homolog, genetically and physically interacts with the yeast FKBP12 prolyl isomerase.

Journal Article Genetics · March 1999 The immunosuppressive drugs FK506 and rapamycin bind to the cellular protein FKBP12, and the resulting FKBP12-drug complexes inhibit signal transduction. FKBP12 is a ubiquitous, highly conserved, abundant enzyme that catalyzes a rate-limiting step in prote ... Full text Link to item Cite

Lic4, a nuclear phosphoprotein that cooperates with calcineurin to regulate cation homeostasis in Saccharomyces cerevisiae.

Journal Article Mol Gen Genet · March 1999 The target of the immunosuppressants cyclosporin A(CsA) and FK506 is calcineurin, a highly conserved protein phosphatase that is required for T-cell activation and the regulation of ion homeostasis in yeast. Here we identify two genes, PMR2B and LIC4 which ... Full text Link to item Cite

R73A and H144Q mutants of the yeast mitochondrial cyclophilin Cpr3 exhibit a low prolyl isomerase activity in both peptide and protein-folding assays.

Journal Article FEBS Lett · January 29, 1999 Previously we reported that the R73A and H144Q variants of the yeast cyclophilin Cpr3 were virtually inactive in a protease-coupled peptide assay, but retained activity as catalysts of a proline-limited protein folding reaction [Scholz, C. et al. (1997) FE ... Full text Link to item Cite

The Cryptococcus neoformans genome sequencing project.

Journal Article Mycopathologia · 1999 Cryptococcus neoformans is a basidiomycete that can cause life-threatening meningoencephalitis in patients with and without impaired immune function. Cryptococcosis is usually an opportunistic infection in patients with compromised immunity as a consequenc ... Full text Link to item Cite

Calcineurin. Structure, function, and inhibition.

Journal Article Cell Biochem Biophys · 1999 Calcineurin is a serine-threonine specific Ca(2+)-calmodulin-activated protein phosphatase that is conserved from yeast to humans. Remarkably, this enzyme is the common target for two novel and structurally unrelated immunosuppressive antifungal drugs, cyc ... Full text Link to item Cite

Regulators of pseudohyphal differentiation in Saccharomyces cerevisiae identified through multicopy suppressor analysis in ammonium permease mutant strains.

Journal Article Genetics · December 1998 Nitrogen-starved diploid cells of the yeast Saccharomyces cerevisiae differentiate into a filamentous, pseudohyphal growth form. Recognition of nitrogen starvation is mediated, at least in part, by the ammonium permease Mep2p and the Galpha subunit Gpa2p. ... Full text Link to item Cite

CNS1 encodes an essential p60/Sti1 homolog in Saccharomyces cerevisiae that suppresses cyclophilin 40 mutations and interacts with Hsp90.

Journal Article Mol Cell Biol · December 1998 Cyclophilins are cis-trans-peptidyl-prolyl isomerases that bind to and are inhibited by the immunosuppressant cyclosporin A (CsA). The toxic effects of CsA are mediated by the 18-kDa cyclophilin A protein. A larger cyclophilin of 40 kDa, cyclophilin 40, is ... Full text Link to item Cite

Signal-transduction cascades as targets for therapeutic intervention by natural products.

Journal Article Trends Biotechnol · October 1998 Many bacteria and fungi produce natural products that are toxic to other microorganisms and have a variety of physiological effects in animals. Recent studies have revealed that, in several cases, the targets of these agents are components of conserved sig ... Full text Link to item Cite

Signal transduction pathways regulating differentiation and pathogenicity of Cryptococcus neoformans.

Journal Article Fungal Genet Biol · October 1998 The basidiomycetous yeast Cryptococcus neoformans is a human pathogen. Several phenotypes of this organism are defined as virulence traits including the polysaccharide capsule, melanin, and the ability to grow at 37 degreesC. The signaling pathways regulat ... Full text Link to item Cite

The MEP2 ammonium permease regulates pseudohyphal differentiation in Saccharomyces cerevisiae.

Journal Article EMBO J · August 10, 1998 In response to nitrogen starvation, diploid cells of the budding yeast Saccharomyces cerevisiae differentiate into a filamentous, pseudohyphal growth form. This dimorphic transition is regulated by the Galpha protein GPA2, by RAS2, and by elements of the p ... Full text Link to item Cite

Rapamycin induces the G0 program of transcriptional repression in yeast by interfering with the TOR signaling pathway.

Journal Article Mol Cell Biol · August 1998 The macrolide antibiotic rapamycin inhibits cellular proliferation by interfering with the highly conserved TOR (for target of rapamycin) signaling pathway. Growth arrest of budding yeast cells treated with rapamycin is followed by the program of molecular ... Full text Link to item Cite

FKBP12 is not required for the modulation of transforming growth factor beta receptor I signaling activity in embryonic fibroblasts and thymocytes.

Journal Article Cell Growth Differ · March 1998 Transforming growth factor beta (TGF-beta) signals through a heteromeric complex of type I and type II transmembrane serine-threonine kinases. Recent evidence suggests that the immunophilin FKBP12 modulates the activity of the type I receptor, based on dat ... Link to item Cite

Immunosuppressants inhibit signal transduction pathways conserved from yeast and pathogenic fungi to man

Journal Article NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY · January 1, 1998 Link to item Cite

Mutational analysis of the function of Met137 and Ile197, two amino acids implicated in sequence-specific DNA recognition by the EcoRI endonuclease.

Journal Article Biol Chem · 1998 The gene encoding the EcoRI endonuclease was altered by site-directed mutagenesis to introduce multiple substitutions of M137 and 1197, two amino acids which were suggested by the revised crystal structure to mediate recognition of the cytosines in the 5'- ... Full text Link to item Cite

Expression, enzyme activity, and subcellular localization of mammalian target of rapamycin in insulin-responsive cells.

Journal Article Biochem Biophys Res Commun · December 29, 1997 The role of the mammalian target of rapamycin (mTOR) was investigated in insulin responsive cell lines. mTOR was expressed at high levels in insulin responsive cell types and in 3T3-L1 cells mTOR expression levels increased dramatically as cells differenti ... Full text Link to item Cite

Temperature-sensitive mutants of the EcoRI endonuclease.

Journal Article J Mol Biol · December 19, 1997 The EcoRI endonuclease is an important recombinant DNA tool and a paradigm of sequence-specific DNA-protein interactions. We have isolated temperature-sensitive (TS) EcoRI endonuclease mutants (R56Q, G78D, P90S, V97I, R105K, M157I, C218Y, A235E, M255I, T26 ... Full text Link to item Cite

Yeast pseudohyphal growth is regulated by GPA2, a G protein alpha homolog.

Journal Article EMBO J · December 1, 1997 Pseudohyphal differentiation, a filamentous growth form of the budding yeast Saccharomyces cerevisiae, is induced by nitrogen starvation. The mechanisms by which nitrogen limitation regulates this process are currently unknown. We have found that GPA2, one ... Full text Link to item Cite

Cryptococcus neoformans mating and virulence are regulated by the G-protein alpha subunit GPA1 and cAMP.

Journal Article Genes Dev · December 1, 1997 This study explores signal transduction pathways that function during mating and infection in the opportunistic, human fungal pathogen Cryptococcus neoformans. The gene encoding a G-protein alpha subunit homolog, GPA1, was disrupted by homologous recombina ... Full text Link to item Cite

GPA1 regulates capsule formation, melanin production, mating, and virulence in Cryptococcus neoformans

Journal Article Clinical Infectious Diseases · December 1, 1997 Virulence of the pathogenic fungus Cryptococcus neoformans is determined by several factors, including the production of a polysaccharide capsule, the elaboration of melanin within the cell wall, and growth at 37°. A gene encoding a cryptococcal G-protein ... Cite

All cyclophilins and FK506 binding proteins are, individually and collectively, dispensable for viability in Saccharomyces cerevisiae.

Journal Article Proc Natl Acad Sci U S A · November 25, 1997 The cyclophilins and FK506 binding proteins (FKBPs) bind to cyclosporin A, FK506, and rapamycin and mediate their immunosuppressive and toxic effects, but the physiological functions of these proteins are largely unknown. Cyclophilins and FKBPs are ubiquit ... Full text Link to item Cite

Functions of FKBP12 and mitochondrial cyclophilin active site residues in vitro and in vivo in Saccharomyces cerevisiae.

Journal Article Mol Biol Cell · November 1997 Cyclophilin and FK506 binding protein (FKBP) accelerate cis-trans peptidyl-prolyl isomerization and bind to and mediate the effects of the immunosuppressants cyclosporin A and FK506. The normal cellular functions of these proteins, however, are unknown. We ... Full text Link to item Cite

STT4 is an essential phosphatidylinositol 4-kinase that is a target of wortmannin in Saccharomyces cerevisiae.

Journal Article J Biol Chem · October 31, 1997 Wortmannin is a natural product that inhibits signal transduction. One target of wortmannin in mammalian cells is the 110-kDa catalytic subunit of phosphatidylinositol 3-kinase (PI 3-kinase). We show that wortmannin is toxic to the yeast Saccharomyces cere ... Full text Link to item Cite

FKBP12 physically and functionally interacts with aspartokinase in Saccharomyces cerevisiae.

Journal Article Mol Cell Biol · October 1997 The peptidyl-prolyl isomerase FKBP12 was originally identified as the intracellular receptor for the immunosuppressive drugs FK506 (tacrolimus) and rapamycin (sirolimus). Although peptidyl-prolyl isomerases have been implicated in catalyzing protein foldin ... Full text Link to item Cite

Cyclophilin active site mutants have native prolyl isomerase activity with a protein substrate.

Journal Article FEBS Lett · September 1, 1997 The prolyl isomerase activity of cyclophilins is traditionally measured by an assay in which prolyl cis/trans isomerization in a chromogenic tetrapeptide is coupled with its isomer-specific cleavage by chymotrypsin. Two variants of mitochondrial cyclophili ... Full text Link to item Cite

Calcineurin is required for virulence of Cryptococcus neoformans.

Journal Article EMBO J · May 15, 1997 Cyclosporin A (CsA) and FK506 are antimicrobial, immunosuppressive natural products that inhibit signal transduction. In T cells and Saccharomyces cerevisiae, CsA and FK506 bind to the immunophilins cyclophilin A and FKBP12 and the resulting complexes inhi ... Full text Link to item Cite

The immunosuppressant FK506 and its nonimmunosuppressive analog L-685,818 are toxic to Cryptococcus neoformans by inhibition of a common target protein.

Journal Article Antimicrob Agents Chemother · January 1997 The immunosuppressant FK506 (tacrolimus) is an antifungal natural product macrolide that suppresses the immune system by blocking T-cell activation. In complex with the intracellular protein FKBP12, FK506 inhibits calcineurin, a Ca(2+)-calmodulin-dependent ... Full text Link to item Cite

Regional bivalent-univalent pairing versus trivalent pairing of a trisomic chromosome in Saccharomyces cerevisiae.

Journal Article Genetics · November 1996 In meiosis I, homologous chromosomes pair, recombine and segregate to opposite poles. These events and subsequent meiosis II ensure that each of the four meiotic products has one complete set of chromosomes. In this study, the meiotic pairing and segregati ... Full text Link to item Cite

Calcineurin mutants render T lymphocytes resistant to cyclosporin A.

Journal Article Mol Pharmacol · September 1996 The immunosuppressants cyclosporin A (CsA) and FK506 have been widely used to prevent and treat graft rejection after human organ and tissue transplantations. CsA and FK506 associate with intracellular binding proteins (i.e., CsA with cyclophilin A and FK5 ... Link to item Cite

Immunosuppressant target protein FKBP12 is required for P-glycoprotein function in yeast.

Journal Article J Biol Chem · August 2, 1996 The mammalian P-glycoprotein (Pgp) is a approximately 170-kDa membrane protein that mediates multidrug resistance in many chemotherapy-resistant tumors by effluxing toxic compounds from the cell. Pgp homologs are expressed in many organisms, from bacteria ... Full text Link to item Cite

Functional expression of the multidrug resistance-associated protein in the yeast Saccharomyces cerevisiae.

Journal Article J Biol Chem · February 23, 1996 The multidrug resistance-associated protein (MRP) is a member of the ATP binding cassette superfamily of transporters which includes the mammalian P-glycoproteins (P-gp) family. In order to facilitate the biochemical and genetic analyses of MRP, we have ex ... Full text Link to item Cite

Mammalian RAFT1 kinase domain provides rapamycin-sensitive TOR function in yeast.

Journal Article Genes Dev · February 1, 1996 In complex with the prolyl isomerase FKBP12, the natural product rapamycin blocks signal transduction in organisms as diverse as yeast and man. The yeast targets of FKBP12-rapamycin, TOR1 and TOR2, are large proteins with homology to lipid and protein kina ... Full text Link to item Cite

FKBP12-rapamycin target TOR2 is a vacuolar protein with an associated phosphatidylinositol-4 kinase activity.

Journal Article EMBO J · December 1, 1995 In complex with the immunophilin FKBP12, the natural product rapamycin inhibits signal transduction events required for G1 to S phase cell cycle progression in yeast and mammalian cells. Genetic studies in yeast first implicated the TOR1 and TOR2 proteins ... Full text Link to item Cite

TOR mutations confer rapamycin resistance by preventing interaction with FKBP12-rapamycin.

Journal Article J Biol Chem · November 17, 1995 The antifungal, immunosuppressive compound rapamycin arrests the cell cycle in G1 in both yeast cells and T-lymphocytes. Previous genetic studies in yeast identified mutations in three genes, FPR1 (FKBP12), TOR1, and TOR2, which confer rapamycin resistance ... Full text Link to item Cite

Molecular mechanisms of immunosuppression by cyclosporine, FK506, and rapamycin.

Journal Article Curr Opin Nephrol Hypertens · November 1995 The immunosuppressant cyclosporine A revolutionized treatment of graft rejection. Two newer agents, FK506 and rapamycin, show great clinical potential. These drugs suppress the immune system by forming protein-drug complexes that interact with and inhibit ... Full text Link to item Cite

vph6 mutants of Saccharomyces cerevisiae require calcineurin for growth and are defective in vacuolar H(+)-ATPase assembly.

Journal Article Genetics · November 1995 We have characterized a Saccharomyces cerevisiae mutant strain that is hypersensitive to cyclosporin A (CsA) and FK506, immunosuppressants that inhibit calcineurin, a serine-threonine-specific phosphatase (PP2B). A single nuclear mutation, designated cev1 ... Full text Link to item Cite

Myristoylation of calcineurin B is not required for function or interaction with immunophilin-immunosuppressant complexes in the yeast Saccharomyces cerevisiae.

Journal Article J Biol Chem · October 20, 1995 Calcineurin is a heterodimeric Ca2+/calmodulin-dependent protein phosphatase that regulates signal transduction and is the target of immunophilin-immunosuppressive drug complexes in T-lymphocytes and in yeast. Calcineurin is composed of a catalytic A subun ... Full text Link to item Cite

Mutations that perturb cyclophilin A ligand binding pocket confer cyclosporin A resistance in Saccharomyces cerevisiae.

Journal Article J Biol Chem · September 8, 1995 In complex with the peptidyl-prolyl isomerase cyclophilin A, the immunosuppressive antifungal drug cyclosporin A (CsA) inhibits a Ca2+/calmodulin-dependent protein phosphatase, calcineurin, which regulates signal transduction. We isolated and characterized ... Full text Link to item Cite

Targets of immunophilin-immunosuppressant complexes are distinct highly conserved regions of calcineurin A.

Journal Article EMBO J · June 15, 1995 The immunosuppressive complexes cyclophilin A-cyclosporin A (CsA) and FKBP12-FK506 inhibit calcineurin, a heterodimeric Ca(2+)-calmodulin-dependent protein phosphatase that regulates signal transduction. We have characterized CsA- or FK506-resistant mutant ... Full text Link to item Cite

Gene disruption with PCR products in Saccharomyces cerevisiae.

Journal Article Gene · May 26, 1995 We describe here the generation of gene disruption constructs using PCR amplification of selectable markers with primers that provide homology to the target gene of interest. We find that regions of homology as short as 38 to 50 bp suffice to mediate homol ... Full text Link to item Cite

Saturation mutagenesis of His114 of EcoRI reveals relaxed-specificity mutants.

Journal Article Gene · May 19, 1995 EcoRI recognizes and cleaves DNA at GAATTC sites and is one of the best characterized sequence-specific restriction endonucleases (ENases). In previous studies, an EcoRI mutant, which exhibited relaxed substrate specificity and cleaved both canonical and E ... Full text Link to item Cite

Role of calcium in T-lymphocyte activation.

Journal Article Adv Second Messenger Phosphoprotein Res · 1995 Full text Link to item Cite

Immunophilins interact with calcineurin in the absence of exogenous immunosuppressive ligands.

Journal Article EMBO J · December 15, 1994 The peptidyl-prolyl isomerases FKBP12 and cyclophilin A (immunophilins) form complexes with the immunosuppressants FK506 and cyclosporin A that inhibit the phosphatase calcineurin. With the yeast two hybrid system, we detect complexes between FKBP12 and th ... Full text Link to item Cite

Yeast as model T cells

Journal Article Perspectives in Drug Discovery and Design · August 1, 1994 The immunosuppressants cyclosporin A, FK-506, and rapamycin prevent T-cell activation by inhibiting intermediate signal transduction steps. Studies have focused on their mechanisms of action, with the aim of both designing novel immunosuppressants and unde ... Full text Cite

Calcineurin is essential in cyclosporin A- and FK506-sensitive yeast strains.

Journal Article Proc Natl Acad Sci U S A · June 7, 1994 The immunophilin-immunosuppressant complexes cyclophilin-cyclosporin A (CsA) and FKBP12-FK506 inhibit the phosphatase calcineurin to block T-cell activation. Although cyclophilin A, FKBP12, and calcineurin are highly conserved from yeast to man, none had p ... Full text Link to item Cite

Quantitation of residual white cells in filtered blood components by polymerase chain reaction amplification of HLA DQ-A DNA.

Journal Article Transfusion · 1994 BACKGROUND: Over the past several years, blood filtration technology has improved dramatically, such that currently available experimental filters are capable of reducing white cells (WBCs) in blood components to less than 0.1 WBC per microL. These residua ... Full text Link to item Cite

Proline isomerases in microorganisms and small eukaryotes.

Journal Article Ann N Y Acad Sci · November 30, 1993 Full text Link to item Cite

The immunosuppressant FK506 inhibits amino acid import in Saccharomyces cerevisiae.

Journal Article Mol Cell Biol · August 1993 The immunosuppressants cyclosporin A, FK506, and rapamycin inhibit growth of unicellular eukaryotic microorganisms and also block activation of T lymphocytes from multicellular eukaryotes. In vitro, these compounds bind and inhibit two different types of p ... Full text Link to item Cite

Tn5-mediated bleomycin resistance in Escherichia coli requires the expression of host genes.

Journal Article Mol Microbiol · June 1993 The transposon Tn5 expresses a gene, ble, whose product increases the viability of Escherichia coli and also confers resistance to the DNA-cleaving antibiotic bleomycin and the DNA-alkylating agent ethylmethanesulphonate. We find that the Ble protein induc ... Full text Link to item Cite

Rapid freezing of whole blood or buffy coat samples for polymerase chain reaction and cell culture analysis: application to detection of human immunodeficiency virus in blood donor and recipient repositories. The Transfusion Safety Study Group.

Journal Article Transfusion · June 1993 Storage of lymphocytes for later use in prospective epidemiologic studies of blood donors and transfusion recipients has been limited by the cost of separating peripheral blood mononuclear cells (PBMCs). When the Transfusion Safety Study began in 1985, it ... Full text Link to item Cite

REPAIR OF DNA SINGLE-STRAND AND DOUBLE-STRAND BREAKS IN ESCHERICHIA-COLI

Journal Article JOURNAL OF CELLULAR BIOCHEMISTRY · February 8, 1993 Link to item Cite

Transplantation and the end-stage renal disease program.

Journal Article Pharos Alpha Omega Alpha Honor Med Soc · 1993 Link to item Cite

Identification of Immunosuppressive Drug Targets in Yeast

Journal Article Methods · January 1, 1993 Cells transfer information from the cell surface to the nucleus via signal transduction pathways. Although much is known about the two ends of such pathways, membrane receptors and nuclear transcription factors, the intermediate steps have remained elusive ... Full text Cite

A yeast cyclophilin gene essential for lactate metabolism at high temperature.

Journal Article Proc Natl Acad Sci U S A · December 1, 1992 The cyclophilins are a family of ubiquitous eukaryotic proteins first identified by high affinity for cyclosporin A (CsA). The immunosuppressant and cytotoxic effects of CsA are thought to result from formation of a toxic complex between cyclophilin and Cs ... Full text Link to item Cite

Allogeneic leukocytes but not therapeutic blood elements induce reactivation and dissemination of latent human immunodeficiency virus type 1 infection: implications for transfusion support of infected patients.

Journal Article Blood · October 15, 1992 Various immunologic stimuli and heterologous viral regulatory elements have been shown to increase susceptibility to, and replication of, human immunodeficiency virus type 1 (HIV-1) in lymphocytes and monocytes in vitro. Transfusion of allogeneic blood com ... Link to item Cite

How the EcoRI endonuclease recognizes and cleaves DNA.

Journal Article Bioessays · July 1992 One popular recombinant DNA tool is the EcoRI endonuclease, which cleaves DNA at GAATTC sites and serves as a paradigm for sequence specific DNA-enzyme interactions. The recently revised X-ray crystal structure of an EcoRI-DNA complex reveals EcoRI employs ... Full text Link to item Cite

Proline isomerases at the crossroads of protein folding, signal transduction, and immunosuppression.

Journal Article New Biol · May 1992 The immunosuppressants cyclosporin A (CsA), FK506, and rapamycin block T-cell activation by interfering with signal transduction. The institution of CsA therapy for prophylaxis against graft rejection revolutionized human organ transplants, and clinical tr ... Link to item Cite

Cyclosporin and asthma.

Journal Article Lancet · April 4, 1992 Link to item Cite

Targets for cell cycle arrest by the immunosuppressant rapamycin in yeast.

Journal Article Science · August 23, 1991 FK506 and rapamycin are related immunosuppressive compounds that block helper T cell activation by interfering with signal transduction. In vitro, both drugs bind and inhibit the FK506-binding protein (FKBP) proline rotamase. Saccharomyces cerevisiae cells ... Full text Link to item Cite

SOS induction as an in vivo assay of enzyme-DNA interactions.

Journal Article Gene · July 15, 1991 We have constructed strains which are convenient and sensitive indicators of DNA damage and describe their use. These strains utilize an SOS::lac Z fusion constructed by Kenyon and Walker [Proc. Natl. Acad. Sci. USA 77 (1980) 2819-2823] and respond to DNA ... Full text Link to item Cite

Nomenclature relating to restriction of modified DNA in Escherichia coli.

Journal Article J Bacteriol · April 1991 At least three restriction systems that attack DNA containing naturally modified bases have been found in common Escherichia coli K-12 strains. These systems are McrA, McrBC, and Mrr. A brief summary of the genetic and phenotypic properties so far observed ... Full text Link to item Cite

Nuclear protein localization.

Journal Article Biochim Biophys Acta · March 7, 1991 Full text Link to item Cite

FK 506-binding protein proline rotamase is a target for the immunosuppressive agent FK 506 in Saccharomyces cerevisiae.

Journal Article Proc Natl Acad Sci U S A · March 1, 1991 FK 506 and cyclosporin A are potent immunosuppressive compounds that inhibit T-cell activation by interfering with signal transduction. In vitro, FK 506 binds and inhibits the activity of FK 506-binding protein (FKBP), a peptidylprolyl rotamase (cis-trans ... Full text Link to item Cite

Mutants of the EcoRI endonuclease with promiscuous substrate specificity implicate residues involved in substrate recognition.

Journal Article EMBO J · October 1990 The EcoRI restriction endonuclease cleaves DNA molecules at the sequence GAATTC. We devised a genetic screen to isolate EcoRI mutants with altered or broadened substrate specificity. In vitro, the purified mutant enzymes cleave both the wild-type substrate ... Full text Link to item Cite

Substrate recognition by the EcoRI endonuclease.

Journal Article Proteins · 1990 The EcoRI restriction endonuclease is one of the most widely used tools for recombinant DNA manipulations. Because the EcoRI enzyme has been extremely well characterized biochemically and its structure is known at 3 A resolution as an enzyme-DNA complex, E ... Full text Link to item Cite

Phage Trojan horses: a conditional expression system for lethal genes.

Journal Article Gene · December 21, 1989 The EcoRI restriction enzyme (ENase) cleaves DNA molecules within the sequence GAATTC. Cells expressing this lethal activity normally make a second enzyme, the M.EcoRI methyltransferase (MTase), which protects their chromosomal DNA by modifying the EcoRI r ... Full text Link to item Cite

Cassettes of the f1 intergenic region.

Journal Article Nucleic Acids Res · June 12, 1989 Full text Link to item Cite

Repair of the Escherichia coli chromosome after in vivo scission by the EcoRI endonuclease.

Journal Article Proc Natl Acad Sci U S A · April 1989 We prepared a set of temperature-sensitive mutants of the EcoRI endonuclease. Under semipermissive conditions, Escherichia coli strains bearing these alleles form poorly growing colonies in which intracellular substrates are cleaved at EcoRI sites and the ... Full text Link to item Cite

Site-specific methylases induce the SOS DNA repair response in Escherichia coli.

Journal Article J Bacteriol · July 1987 Expression of the site-specific adenine methylase HhaII (GmeANTC, where me is methyl) or PstI (CTGCmeAG) induced the SOS DNA repair response in Escherichia coli. In contrast, expression of methylases indigenous to E. coli either did not induce SOS (EcoRI [ ... Full text Link to item Cite