Scholars@Duke
Jennifer L Tenor

Jennifer L Tenor

Assistant Professor in Medicine
Medicine, Infectious Diseases
jennifer.tenor@duke.edu
Box 102359, 303 Research Drive, Sands Building, Room, Durham, NC 27710
303 Research Drive, 337/ Sands Bldg, Durham, NC 27710

Selected Publications

Integration of genomic and pharmacokinetic data to predict clinical outcomes in HIV-associated cryptococcal meningitis.

Journal Article mBio · October 16, 2024 UNLABELLED: Cryptococcal meningitis causes an estimated 112,000 global deaths per annum. Genomic and phenotypic features of the infecting strain of Cryptococcus spp. have been associated with outcomes from cryptococcal meningitis. Additionally, population- ... Full text Link to item Cite

Structures of trehalose-6-phosphate synthase, Tps1, from the fungal pathogen Cryptococcus neoformans: A target for antifungals.

Journal Article Proc Natl Acad Sci U S A · August 6, 2024 Invasive fungal diseases are a major threat to human health, resulting in more than 1.5 million annual deaths worldwide. The arsenal of antifungal therapeutics remains limited and is in dire need of drugs that target additional biosynthetic pathways that a ... Full text Link to item Cite

Efficacy of Liposomal Nystatin in a Rabbit Model of Cryptococcal Meningitis.

Journal Article J Fungi (Basel) · July 26, 2024 Cryptococcal meningitis (CM) causes significant global morbidity and mortality. Current therapeutic strategies rely on deoxycholated or liposomal forms of the polyene amphotericin B. Nystatin is also a polyene with broad-spectrum antimicrobial activity. Tr ... Full text Link to item Cite

A ketogenic diet enhances fluconazole efficacy in murine models of systemic fungal infection.

Journal Article mBio · May 8, 2024 Invasive fungal infections are a significant public health concern, with mortality rates ranging from 20% to 85% despite current treatments. Therefore, we examined whether a ketogenic diet could serve as a successful treatment intervention in murine models ... Full text Link to item Cite

Biolistic Transformation of Cryptococcus neoformans.

Journal Article Methods Mol Biol · 2024 Biolistic transformation of Cryptococcus neoformans is used as a molecular tool to genetically alter or delete targeted genes. The DNA is introduced into the yeast on DNA-coated gold beads by a helium shock wave produced using a biolistic particle system. ... Full text Link to item Cite

Cryptococcus neoformans trehalose-6-phosphate synthase (tps1) promotes organ-specific virulence and fungal protection against multiple lines of host defenses.

Journal Article Front Cell Infect Microbiol · 2024 Trehalose-6-phosphate synthase (TPS1) was identified as a virulence factor for Cryptococcus neoformans and a promising therapeutic target. This study reveals previously unknown roles of TPS1 in evasion of host defenses during pulmonary and disseminated pha ... Full text Link to item Cite

Genetic diversity and microevolution in clinical Cryptococcus isolates from Cameroon.

Journal Article Med Mycol · December 1, 2023 Cryptococcal meningitis is the second most common cause of death in people living with HIV/AIDS, yet we have a limited understanding of how cryptococcal isolates change over the course of infection. Cryptococcal infections are environmentally acquired, and ... Full text Link to item Cite

Pharmacodynamics of ATI-2307 in a rabbit model of cryptococcal meningoencephalitis.

Journal Article Antimicrob Agents Chemother · October 18, 2023 Cryptococcal meningoencephalitis (CM) is a devastating fungal disease with high morbidity and mortality. The current regimen that is standard-of-care involves a combination of three different drugs administered for up to one year. There is a critical need ... Full text Link to item Cite

Susceptibility to Cryptococcus neoformans Infection with Bruton's Tyrosine Kinase Inhibition.

Journal Article Infect Immun · August 16, 2023 Patients receiving the Bruton's tyrosine kinase (BTK) inhibitor ibrutinib have an increased likelihood of fungal infections. The objectives of this study were to determine if Cryptococcus neoformans infection severity was isolate dependent with BTK inhibit ... Full text Link to item Cite

Efficacy of APX2039 in a Rabbit Model of Cryptococcal Meningitis.

Journal Article mBio · December 20, 2022 Cryptococcal Meningitis (CM) is uniformly fatal if not treated, and treatment options are limited. We previously reported on the activity of APX2096, the prodrug of the novel Gwt1 inhibitor APX2039, in a mouse model of CM. Here, we investigated the efficac ... Full text Link to item Cite

Genomic Variation across a Clinical Cryptococcus Population Linked to Disease Outcome.

Journal Article mBio · December 20, 2022 Cryptococcus neoformans is the causative agent of cryptococcosis, a disease with poor patient outcomes that accounts for approximately 180,000 deaths each year. Patient outcomes may be impacted by the underlying genetics of the infecting isolate; however, ... 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

Gene Expression of Diverse Cryptococcus Isolates during Infection of the Human Central Nervous System.

Journal Article mBio · December 2021 Cryptococcus neoformans is a major human central nervous system (CNS) fungal pathogen causing considerable morbidity and mortality. In this study, we provide the widest view to date of the yeast transcriptome directly from the human subarachnoid space and ... Full text Cite

Amoeba Predation of Cryptococcus neoformans Results in Pleiotropic Changes to Traits Associated with Virulence.

Journal Article mBio · April 27, 2021 Amoeboid predators, such as amoebae, are proposed to select for survival traits in soil microbes such as Cryptococcus neoformans; these traits can also function in animal virulence by defeating phagocytic immune cells, such as macrophages. Consistent with ... Full text Link to item Cite

Comparison of Cryptococcus gattii/neoformans Species Complex to Related Genera (Papiliotrema and Naganishia) Reveal Variances in Virulence Associated Factors and Antifungal Susceptibility.

Journal Article Front Cell Infect Microbiol · 2021 Cryptococcosis is an infectious disease of worldwide distribution, caused by encapsulated yeasts belonging to the phylum Basidiomycota. The genus Cryptococcus includes several species distributed around the world. The C. gattii/neoformans species complex i ... Full text Link to item Cite

Assessing the virulence of Cryptococcus neoformans causing meningitis in HIV infected and uninfected patients in Vietnam.

Journal Article Med Mycol · November 10, 2020 We previously observed a substantial burden of cryptococcal meningitis in Vietnam atypically arising in individuals who are uninfected with human immunodeficiency virus (HIV). This disease was associated with a single genotype of Cryptococcus neoformans (s ... Full text Link to item Cite

Landscape of gene expression variation of natural isolates of Cryptococcus neoformans in response to biologically relevant stresses.

Journal Article Microb Genom · January 2020 Cryptococcus neoformans is an opportunistic fungal pathogen that at its peak epidemic levels caused an estimated million cases of cryptococcal meningitis per year worldwide. This species can grow in diverse environmental (trees, soil and bird excreta) and ... Full text Link to item Cite

Regulatory Mechanism of the Atypical AP-1-Like Transcription Factor Yap1 in Cryptococcus neoformans.

Journal Article mSphere · November 20, 2019 AP-1-like transcription factors play evolutionarily conserved roles as redox sensors in eukaryotic oxidative stress responses. In this study, we aimed to elucidate the regulatory mechanism of an atypical yeast AP-1-like protein, Yap1, in the stress respons ... Full text Link to item Cite

Genotypic diversity and clinical outcome of cryptococcosis in renal transplant recipients in Brazil.

Journal Article Emerg Microbes Infect · 2019 Genotypic diversity and fluconazole susceptibility of 82 Cryptococcus neoformans and Cryptococcus gattii isolates from 60 renal transplant recipients in Brazil were characterized. Clinical characteristics of the patients and prognostic factors were analyse ... Full text Link to item Cite

In Vitro and In Vivo Evaluation of APX001A/APX001 and Other Gwt1 Inhibitors against Cryptococcus.

Journal Article Antimicrob Agents Chemother · August 2018 Cryptococcal meningitis (CM), caused primarily by Cryptococcus neoformans, is uniformly fatal if not treated. Treatment options are limited, especially in resource-poor geographical regions, and mortality rates remain high despite current therapies. Here w ... Full text Link to item Cite

Structural and In Vivo Studies on Trehalose-6-Phosphate Synthase from Pathogenic Fungi Provide Insights into Its Catalytic Mechanism, Biological Necessity, and Potential for Novel Antifungal Drug Design.

Journal Article mBio · July 25, 2017 The disaccharide trehalose is critical to the survival of pathogenic fungi in their human host. Trehalose-6-phosphate synthase (Tps1) catalyzes the first step of trehalose biosynthesis in fungi. Here, we report the first structures of eukaryotic Tps1s in c ... 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

Microevolution of Serial Clinical Isolates of Cryptococcus neoformans var. grubii and C. gattii.

Journal Article mBio · March 7, 2017 The pathogenic species of Cryptococcus are a major cause of mortality owing to severe infections in immunocompromised as well as immunocompetent individuals. Although antifungal treatment is usually effective, many patients relapse after treatment, and in ... Full text Open Access Link to item Cite

Trehalose pathway as an antifungal target.

Journal Article Virulence · February 17, 2017 With an increasing immunocompromised population which is linked to invasive fungal infections, it is clear that our present 3 classes of antifungal agents may not be sufficient to provide optimal management to these fragile patients. Furthermore, with wide ... Full text Link to item Cite

Live Imaging of Host-Parasite Interactions in a Zebrafish Infection Model Reveals Cryptococcal Determinants of Virulence and Central Nervous System Invasion.

Journal Article mBio · September 29, 2015 UNLABELLED: The human fungal pathogen Cryptococcus neoformans is capable of infecting a broad range of hosts, from invertebrates like amoebas and nematodes to standard vertebrate models such as mice and rabbits. Here we have taken advantage of a zebrafish ... Full text Open Access Link to item Cite

The Cryptococcus neoformans transcriptome at the site of human meningitis

Journal Article mBio · February 4, 2014 Cryptococcus neoformans is the leading cause of fungal meningitis worldwide. Previous studies have characterized the cryptococcal transcriptome under various stress conditions, but a comprehensive profile of the C. neoformans transcriptome in the human hos ... Full text Cite

Nitrogen source-dependent capsule induction in human-pathogenic cryptococcus species.

Journal Article Eukaryot Cell · November 2013 Cryptococcus neoformans and C. gattii cause meningoencephalitis and are an increasing human health threat. These pathogenic Cryptococcus species are neurotropic and persist in the cerebrospinal fluid (CSF) of the mammalian host during infection. In order t ... Full text Link to item Cite

Pleiotropic effects of deubiquitinating enzyme Ubp5 on growth and pathogenesis of Cryptococcus neoformans.

Journal Article PLoS One · 2012 Ubiquitination is a reversible protein modification that influences various cellular processes in eukaryotic cells. Deubiquitinating enzymes remove ubiquitin, maintain ubiquitin homeostasis and regulate protein degradation via the ubiquitination pathway. C ... Full text Link to item Cite

Survival defects of Cryptococcus neoformans mutants exposed to human cerebrospinal fluid result in attenuated virulence in an experimental model of meningitis.

Journal Article Infect Immun · October 2010 Cryptococcus neoformans is a fungal pathogen that encounters various microenvironments during growth in the mammalian host, including intracellular vacuoles, blood, and cerebrospinal fluid (CSF). Because the CSF is isolated by the blood-brain barrier, we h ... Full text Link to item Cite

A conserved PMK-1/p38 MAPK is required in caenorhabditis elegans tissue-specific immune response to Yersinia pestis infection.

Journal Article J Biol Chem · April 2, 2010 Yersinia pestis has acquired a variety of complex strategies that enable the bacterium to overcome defenses in different hosts and ensure its survival and successful transmission. A full-genome microarray analysis on Caenorhabditis elegans infected with Y. ... Full text Link to item Cite

A conserved Toll-like receptor is required for Caenorhabditis elegans innate immunity.

Journal Article EMBO Rep · January 2008 Pathogen recognition through Toll-like receptors (TLRs) is crucial in order to mount an appropriate immune response against microorganisms. On the basis of a lack of evidence indicating that Caenorhabditis elegans uses TLRs to elicit an immune response and ... Full text Link to item Cite

Caenorhabditis elegans-based screen identifies Salmonella virulence factors required for conserved host-pathogen interactions.

Journal Article Curr Biol · June 8, 2004 A Caenorhabditis elegans-Salmonella enterica host-pathogen model was used to identify both novel and previously known S. enterica virulence factors (HilA, HilD, InvH, SptP, RhuM, Spi4-F, PipA, VsdA, RepC, Sb25, RfaL, GmhA, LeuO, CstA, and RecC), including ... Full text Link to item Cite

Colonial differentiation in Streptomyces coelicolor depends on translation of a specific codon within the adpA gene.

Journal Article J Bacteriol · December 2003 We identified adpA as an araC-like regulatory gene needed for colonial morphogenesis in Streptomyces coelicolor and showed that its activity depended on a unique TTA triplet corresponding to the leucyl-tRNA gene (bldA). These findings partially explained t ... Full text Link to item Cite

A connection between stress and development in the multicellular prokaryote Streptomyces coelicolor A3(2).

Journal Article Mol Microbiol · May 2001 Morphological changes leading to aerial mycelium formation and sporulation in the mycelial bacterium Streptomyces coelicolor rely on establishing distinct patterns of gene expression in separate regions of the colony. sigmaH was identified previously as on ... Full text Link to item Cite