James Andrew Alspaugh II

Journal Article mBio · October 16, 2024 UNLABELLED: Cellular responses to external stress allow microorganisms to adapt to a vast array of environmental conditions, including infection sites. The molecular mechanisms behind these responses are studied to gain insight into microbial pathogenesis, ... 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

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

Preprint · July 11, 2024 Full text Link to item Cite

CryptoCEN: A Co-Expression Network for Cryptococcus neoformans reveals novel proteins involved in DNA damage repair.

Journal Article PLoS Genet · February 2024 Elucidating gene function is a major goal in biology, especially among non-model organisms. However, doing so is complicated by the fact that molecular conservation does not always mirror functional conservation, and that complex relationships among genes ... Full text Link to item Cite

Measuring Stress Phenotypes in Cryptococcus neoformans.

Journal Article Methods Mol Biol · 2024 Cryptococcus neoformans is an opportunistic human fungal pathogen capable of surviving in a wide range of environments and hosts. It has been developed as a model organism to study fungal pathogenesis due to its fully sequenced haploid genome and optimized ... Full text Link to item Cite

CryptoCEN: A Co-Expression Network for Cryptococcus neoformans reveals novel proteins involved in DNA damage repair.

Preprint · August 18, 2023 Full text Link to item Cite

A fungal lytic polysaccharide monooxygenase is required for cell wall integrity, thermotolerance, and virulence of the fungal human pathogen Cryptococcus neoformans.

Journal Article PLoS Pathog · April 2023 Fungi often adapt to environmental stress by altering their size, shape, or rate of cell division. These morphological changes require reorganization of the cell wall, a structural feature external to the cell membrane composed of highly interconnected pol ... Full text Link to item Cite

Cryptococcus neoformans Mar1 function links mitochondrial metabolism, oxidative stress, and antifungal tolerance.

Journal Article Front Physiol · 2023 Introduction: Microbial pathogens undergo significant physiological changes during interactions with the infected host, including alterations in metabolism and cell architecture. The Cryptococcus neoformans Mar1 protein is required for the proper ordering ... Full text Link to item Cite

Extension of O-Linked Mannosylation in the Golgi Apparatus Is Critical for Cell Wall Integrity Signaling and Interaction with Host Cells in Cryptococcus neoformans Pathogenesis.

Journal Article mBio · December 20, 2022 The human-pathogenic yeast Cryptococcus neoformans assembles two types of O-linked glycans on its proteins. In this study, we identified and functionally characterized the C. neoformans CAP6 gene, encoding an α1,3-mannosyltransferase responsible for the se ... Full text Link to item Cite

Structure-Guided Discovery of Potent Antifungals that Prevent Ras Signaling by Inhibiting Protein Farnesyltransferase.

Journal Article J Med Chem · October 27, 2022 Infections by fungal pathogens are difficult to treat due to a paucity of antifungals and emerging resistances. Next-generation antifungals therefore are needed urgently. We have developed compounds that prevent farnesylation of Cryptoccoccus neoformans Ra ... Full text Link to item Cite

Engineered Fluorescent Strains of Cryptococcus neoformans: a Versatile Toolbox for Studies of Host-Pathogen Interactions and Fungal Biology, Including the Viable but Nonculturable State.

Journal Article Microbiol Spectr · October 26, 2022 Cryptococcus neoformans is an opportunistic fungal pathogen known for its remarkable ability to infect and subvert phagocytes. This ability provides survival and persistence within the host and relies on phenotypic plasticity. The viable but nonculturable ... Full text Link to item Cite

The Cryptococcus neoformans Flc1 Homologue Controls Calcium Homeostasis and Confers Fungal Pathogenicity in the Infected Hosts.

Journal Article mBio · October 26, 2022 Cryptococcus neoformans, an opportunistic yeast pathogen, relies on a complex network of stress response pathways that allow for proliferation in the host. In Saccharomyces cerevisiae, stress responses are regulated by integral membrane proteins containing ... Full text Link to item Cite

An Immunogenic and Slow-Growing Cryptococcal Strain Induces a Chronic Granulomatous Infection in Murine Lungs.

Journal Article Infect Immun · June 16, 2022 Many successful pathogens cause latent infections, remaining dormant within the host for years but retaining the ability to reactivate to cause symptomatic disease. The human opportunistic fungal pathogen Cryptococcus neoformans establishes latent pulmonar ... Full text Link to item Cite

Interactions between copper homeostasis and the fungal cell wall affect copper stress resistance.

Journal Article PLoS Pathog · June 2022 Copper homeostasis mechanisms are essential for microbial adaption to changing copper levels within the host during infection. In the opportunistic fungal pathogen Cryptococcus neoformans (Cn), the Cn Cbi1/Bim1 protein is a newly identified copper binding ... Full text Link to item Cite

Transcriptional Profiles Elucidate Differential Host Responses to Infection with Cryptococcus neoformans and Cryptococcus gattii.

Journal Article J Fungi (Basel) · April 22, 2022 Many aspects of the host response to invasive cryptococcal infections remain poorly understood. In order to explore the pathobiology of infection with common clinical strains, we infected BALB/cJ mice with Cryptococcus neoformans, Cryptococcus gattii, or s ... Full text Link to item Cite

Anti-cryptococcal activity of preussolides A and B, phosphoethanolamine-substituted 24-membered macrolides, and leptosin C from coprophilous isolates of Preussia typharum.

Journal Article J Ind Microbiol Biotechnol · December 23, 2021 Cryptococcus neoformans is a serious human pathogen with limited options for treatment. We have interrogated extracts from fungal fermentations to find Cryptococcus-inhibiting natural products using assays for growth inhibition and differential thermosensi ... Full text Link to item Cite

Comparative analysis of RNA enrichment methods for preparation of Cryptococcus neoformans RNA sequencing libraries.

Journal Article G3 (Bethesda) · October 19, 2021 RNA sequencing (RNA-Seq) experiments focused on gene expression involve removal of ribosomal RNA (rRNA) because it is the major RNA constituent of cells. This process, called RNA enrichment, is done primarily to reduce cost: without rRNA removal, deeper se ... Full text Link to item Cite

Comparative analysis of RNA enrichment methods for preparation ofCryptococcus neoformansRNA sequencing libraries

Journal Article · 2021 ABSTRACT Ribosomal RNA (rRNA) is the major RNA constituent of cells, therefore most RNA sequencing (RNA-Seq) experiments involve removal of rRNA. This process, called RNA enrichment, is done primarily to reduce cost: without rRNA removal, deeper s ... Full text Cite

A hyper-immunogenic and slow-growing fungal strain induces a murine granulomatous response to cryptococcal infection

Journal Article · 2021 ABSTRACT Many successful pathogens cause latent infections, remaining dormant within the host for years but retaining the ability to reactivate to cause symptomatic disease. The human opportunistic pathogen Cryptococcus neoformans is a ubiquitous ... Full text Cite

Adaptive changes in the fungal cell wall mediate copper homeostasis

Journal Article · 2021 Copper homeostasis mechanisms are essential for microbial adaption to changing copper levels within the host during infection. In the opportunistic fungal pathogen Cryptococcus neoformans ( Cn ), the Cn Cbi1/Bim1 protein is a newly identified copper bindin ... Full text Cite

Campafungins: Inhibitors of Candida albicans and Cryptococcus neoformans Hyphal Growth.

Journal Article J Nat Prod · September 25, 2020 Campafungin A is a polyketide that was recognized in the Candida albicans fitness test due to its antiproliferative and antihyphal activity. Its mode of action was hypothesized to involve inhibition of a cAMP-dependent PKA pathway. The originally proposed ... Full text Open Access Link to item Cite

Sphaerostilbellins, New Antimicrobial Aminolipopeptide Peptaibiotics from Sphaerostilbella toxica.

Journal Article Biomolecules · September 2020 Sphaerostilbella toxica is a mycoparasitic fungus that can be found parasitizing wood-decay basidiomycetes in the southern USA. Organic solvent extracts of fermented strains of S. toxica exhibited potent antimicrobial activity, including pote ... Full text Cite

Erg6 affects membrane composition and virulence of the human fungal pathogen Cryptococcus neoformans.

Journal Article Fungal Genet Biol · July 2020 Ergosterol is the most important membrane sterol in fungal cells and a component not found in the membranes of human cells. We identified the ERG6 gene in the AIDS-associated fungal pathogen, Cryptococcus neoformans, encoding the sterol C-24 methyltransfer ... Full text Link to item Cite

Sterol-Response Pathways Mediate Alkaline Survival in Diverse Fungi.

Journal Article mBio · June 16, 2020 The ability for cells to maintain homeostasis in the presence of extracellular stress is essential for their survival. Stress adaptations are especially important for microbial pathogens to respond to rapidly changing conditions, such as those encountered ... Full text 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

Human IgM Inhibits the Formation of Titan-Like Cells in Cryptococcus neoformans.

Journal Article Infect Immun · March 23, 2020 Human studies have shown associations between cryptococcal meningitis and reduced IgM memory B cell levels, and studies in IgM- and/or B cell-deficient mice have demonstrated increased Cryptococcus neoformans dissemination from lungs to brain. Since immuno ... Full text Link to item Cite

New Spins on Old Drugs: Enhancing Activity of Antifungals.

Journal Article Cell Chem Biol · March 19, 2020 In this issue of Cell Chemical Biology, Caplan et al. (2020) describe a series of studies in the human fungal pathogen Candida albicans to identify a new target for antimicrobial drug development. Beginning with an unbiased compound screen, they identify n ... Full text Link to item Cite

Length Specificity and Polymerization Mechanism of (1,3)-β-d-Glucan Synthase in Fungal Cell Wall Biosynthesis.

Journal Article Biochemistry · February 11, 2020 (1,3)-β-d-Glucan synthase (GS) catalyzes formation of the linear (1,3)-β-d-glucan in the fungal cell wall and is a target of clinically approved antifungal antibiotics. The catalytic subunit of GS, FKS protein, does not exhibit significant sequence homolog ... Full text Link to item Cite

Chitin: A "Hidden Figure" in the Fungal Cell Wall.

Journal Article Curr Top Microbiol Immunol · 2020 Chitin and chitosan are two related polysaccharides that provide important structural stability to fungal cell walls. Often embedded deeply within the cell wall structure, these molecules anchor other components at the cell surface. Chitin-directed organiz ... 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

Sterol-response pathways mediate alkaline survival in diverse fungi

Journal Article · 2020 The ability for cells to maintain homeostasis in the presence of extracellular stress is essential for their survival. Stress adaptations are especially important for microbial pathogens to respond to rapidly changing conditions, such as those encountered ... Full text Cite

Identification of the Antifungal Metabolite Chaetoglobosin P From Discosia rubi Using a Cryptococcus neoformans Inhibition Assay: Insights Into Mode of Action and Biosynthesis.

Journal Article Front Microbiol · 2020 Cryptococcus neoformans is an important human pathogen with limited options for treatments. We have interrogated extracts from fungal fermentations to find Cryptococcus-inhibiting natural products using assays for growth inhibition, differential thermosens ... Full text Open Access Link to item Cite

A Fungal Arrestin Protein Contributes to Cell Cycle Progression and Pathogenesis.

Journal Article mBio · November 19, 2019 Arrestins, a structurally specialized and functionally diverse group of proteins, are central regulators of adaptive cellular responses in eukaryotes. Previous studies on fungal arrestins have demonstrated their capacity to modulate diverse cellular proces ... Full text Link to item Cite

Roles for Stress Response and Cell Wall Biosynthesis Pathways in Caspofungin Tolerance in Cryptococcus neoformans.

Journal Article Genetics · September 2019 Limited antifungal diversity and availability are growing problems for the treatment of fungal infections in the face of increasing drug resistance. The echinocandins, one of the newest classes of antifungal drugs, inhibit production of a crucial cell wall ... Full text Link to item Cite

A Multi-Institution Collaboration to Define Core Content and Design Flexible Curricular Components for a Foundational Medical School Course: Implications for National Curriculum Reform.

Journal Article Acad Med · June 2019 Medical educators have not reached widespread agreement on core content for a U.S. medical school curriculum. As a first step toward addressing this, five U.S. medical schools formed the Robert Wood Johnson Foundation Reimagining Medical Education collabor ... Full text Link to item Cite

Wortmannin and Wortmannine Analogues from an Undescribed Niesslia sp.

Journal Article J Nat Prod · March 22, 2019 In the course of our studies of coprophilous fungi as sources of antifungal agents, a strain of an undescribed species in the genus Niesslia (TTI-0426) was isolated from horse dung collected in Texas. An extract from fermentation cultures of this strain af ... Full text Link to item Cite

A fungal arrestin protein contributes to cell cycle progression and pathogenesis

Journal Article · 2019 ABSTRACT Arrestins, a structurally specialized and functionally diverse group of proteins, are central regulators of adaptive cellular responses in eukaryotes. Previous studies on fungal arrestins have demonstrated their capacity to modulate diver ... Full text Cite

Identifying a novel connection between the fungal plasma membrane and pH-sensing.

Journal Article Mol Microbiol · August 2018 The mechanisms by which micro-organisms sense and internalize extracellular pH signals are not completely understood. One example of a known external pH-sensing process is the fungal-specific Rim/Pal signal transduction pathway. Fungi, such as the opportun ... Full text Open Access Link to item Cite

Characterization of additional components of the environmental pH-sensing complex in the pathogenic fungus Cryptococcus neoformans.

Journal Article J Biol Chem · June 29, 2018 Pathogenic microorganisms must adapt to changes in their immediate surroundings, including alterations in pH, to survive the shift from the external environment to that of the infected host. In the basidiomycete fungal pathogen Cryptococcus neoformans, the ... Full text Open Access Link to item Cite

Defects in intracellular trafficking of fungal cell wall synthases lead to aberrant host immune recognition.

Journal Article PLoS Pathog · June 2018 The human fungal pathogen, Cryptococcus neoformans, dramatically alters its cell wall, both in size and composition, upon entering the host. This cell wall remodeling is essential for host immune avoidance by this pathogen. In a genetic screen for mutants ... Full text Open Access Link to item Cite

HDAC genes play distinct and redundant roles in Cryptococcus neoformans virulence.

Journal Article Sci Rep · March 26, 2018 The human fungal pathogen Cryptococcus neoformans undergoes many phenotypic changes to promote its survival in specific ecological niches and inside the host. To explore the role of chromatin remodeling on the expression of virulence-related traits, we ide ... Full text Open Access Link to item Cite

Identification of cyclosporin C from Amphichorda felina using a Cryptococcus neoformans differential temperature sensitivity assay.

Journal Article Appl Microbiol Biotechnol · March 2018 We used a temperature differential assay with the opportunistic fungal pathogen Cryptococcus neoformans as a simple screening platform to detect small molecules with antifungal activity in natural product extracts. By screening of a collection extracts fro ... Full text Open Access Link to item Cite

Cryptococcal pathogenic mechanisms: a dangerous trip from the environment to the brain.

Journal Article Mem Inst Oswaldo Cruz · 2018 Cryptococcus neoformans is an opportunistic pathogenic yeast that causes serious infections, most commonly of the central nervous system (CNS). C. neoformans is mainly found in the environment and acquired by inhalation. It could be metaphorically imagined ... Full text Link to item Cite

A Wor1-Like Transcription Factor Is Essential for Virulence of Cryptococcus neoformans.

Journal Article Front Cell Infect Microbiol · 2018 Gti1/Pac2 transcription factors occur exclusively in fungi and their roles vary according to species, including regulating morphological transition and virulence, mating and secondary metabolism. Many of these functions are important for fungal pathogenesi ... Full text Open Access Link to item Cite

Disseminated Adenovirus Infection After Combined Liver-Kidney Transplantation.

Journal Article Front Cell Infect Microbiol · 2018 Human adenovirus (HAdV) infections are well-described after hematopoietic stem cell transplantation but less well understood in solid organ transplantation (SOT). We describe a case of disseminated HAdV type 21 infection 5 months after combined liver-kidne ... Full text Open Access Link to item Cite

Targeting protein localization for anti-infective therapy.

Journal Article Virulence · October 3, 2017 Full text Link to item Cite

Rim Pathway-Mediated Alterations in the Fungal Cell Wall Influence Immune Recognition and Inflammation.

Journal Article mBio · January 31, 2017 UNLABELLED: Compared to other fungal pathogens, Cryptococcus neoformans is particularly adept at avoiding detection by innate immune cells. To explore fungal cellular features involved in immune avoidance, we characterized cell surface changes of the C. ne ... Full text Link to item Cite

The role of Aspartyl aminopeptidase (Ape4) in Cryptococcus neoformans virulence and authophagy.

Journal Article PLoS One · 2017 In order to survive and cause disease, microbial pathogens must be able to proliferate at the temperature of their infected host. We identified novel microbial features associated with thermotolerance in the opportunistic fungal pathogen Cryptococcus neofo ... Full text Link to item Cite

Discovery of Ibomycin, a Potent Antifungal Weapon.

Journal Article Cell Chem Biol · November 17, 2016 In this issue of Cell Chemical Biology, Robbins et al. (2016) identify ibomycin, a unique compound with antifungal activity. Microbial physiological and genetic studies suggest that endocytic trafficking might be the site of action for this lead antifungal ... Full text Open Access Link to item Cite

New Horizons in Antifungal Therapy.

Journal Article J Fungi (Basel) · October 2, 2016 Recent investigations have yielded both profound insights into the mechanisms required by pathogenic fungi for virulence within the human host, as well as novel potential targets for antifungal therapeutics. Some of these studies have resulted in the ident ... Full text Link to item Cite

Unveiling Protein Kinase A Targets in Cryptococcus neoformans Capsule Formation.

Journal Article mBio · February 9, 2016 The protein kinase A (PKA) signal transduction pathway has been associated with pathogenesis in many fungal species. Geddes and colleagues [mBio 7(1):e01862-15, 2016, doi:10.1128/mBio.01862-15] used quantitative proteomics approaches to define proteins wit ... Full text Open Access Link to item Cite

Relative Contributions of Prenylation and Postprenylation Processing in Cryptococcus neoformans Pathogenesis.

Journal Article mSphere · 2016 Prenyltransferase enzymes promote the membrane localization of their target proteins by directing the attachment of a hydrophobic lipid group at a conserved C-terminal CAAX motif. Subsequently, the prenylated protein is further modified by postprenylation ... Full text Open Access Link to item Cite

Rapid mapping of insertional mutations to probe cell wall regulation in Cryptococcus neoformans.

Journal Article Fungal Genet Biol · September 2015 Random insertional mutagenesis screens are important tools in microbial genetics studies. Investigators in fungal systems have used the plant pathogen Agrobacterium tumefaciens to create tagged, random mutations for genetic screens in their fungal species ... Full text Link to item Cite

Impact of Protein Palmitoylation on the Virulence Potential of Cryptococcus neoformans.

Journal Article Eukaryot Cell · July 2015 The localization and specialized function of Ras-like proteins are largely determined by posttranslational processing events. In a highly regulated process, palmitoyl groups may be added to C-terminal cysteine residues, targeting these proteins to specific ... Full text Link to item Cite

Virulence mechanisms and Cryptococcus neoformans pathogenesis.

Journal Article Fungal Genet Biol · May 2015 The human fungal pathogen Cryptococcus neoformans is able to rapidly and effectively adapt to varying conditions, favoring its survival in the environment and in the infected host. Many microbial phenotypes have been specifically correlated with virulence ... Full text Link to item Cite

The Cryptococcus neoformans alkaline response pathway: identification of a novel rim pathway activator.

Journal Article PLoS Genet · April 2015 The Rim101/PacC transcription factor acts in a fungal-specific signaling pathway responsible for sensing extracellular pH signals. First characterized in ascomycete fungi such as Aspergillus nidulans and Saccharomyces cerevisiae, the Rim/Pal pathway mainta ... Full text Link to item Cite

Fungal morphogenesis.

Journal Article Cold Spring Harb Perspect Med · November 3, 2014 Morphogenesis in fungi is often induced by extracellular factors and executed by fungal genetic factors. Cell surface changes and alterations of the microenvironment often accompany morphogenetic changes in fungi. In this review, we will first discuss the ... Full text Link to item Cite

The role of the de novo pyrimidine biosynthetic pathway in Cryptococcus neoformans high temperature growth and virulence.

Journal Article Fungal Genet Biol · September 2014 Fungal infections are often difficult to treat due to the inherent similarities between fungal and animal cells and the resulting host toxicity from many antifungal compounds. Cryptococcus neoformans is an opportunistic fungal pathogen of humans that cause ... Full text Link to item Cite