ArticleGenetics2022
Genetic analysis of Hsp90 function in Cryptococcus neoformans highlights key roles in stress tolerance and virulence.
Article in Genetics, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 39 citations in OpenAlex.
- Heat Shock Proteins in Medically Relevant Fungal Pathogens: From Molecular Chaperones to Virulence Factors and Therapeutic Targets.Journal of fungi (Basel, Switzerland) · 2026Review
- Current and emerging therapies for fungal biofilms and systemic infections.Critical reviews in microbiology · 2026Review
- Does the use of topical azoles have an impact on antifungal resistance?The Journal of antimicrobial chemotherapy · 2025Article
- Global proteomic analysis ofmSystems · 2025Article
- Pathogenic Fungal Sensing and Responses to Stressful Host Environments.Annual review of microbiology · 2025Review
- Expansion of the functional genomics GRACE library reveals genes relevant for temperature-dependent fitness in Candida albicans.PLoS biology · 2025Article
- Reduced growth and biofilm formation at high temperatures contribute to Cryptococcus deneoformans dermatotropism.Disease models & mechanisms · 2025Article
- Insights from Mass Spectrometry-Based Proteomics onJournal of fungi (Basel, Switzerland) · 2025Review
- Disruption of the ATP-dependent unfoldase ClpX reverses antifungal resistance in Cryptococcus neoformans.Nature communications · 2025Article
- Adaptation of the tetracycline-repressible system for modulating the expression of essential genes inmSphere · 2025Article
- The genome of the polyextremophilic yeast, Naganishia friedmannii, reveals adaptations involved in stress response pathways, carbohydrate metabolism expansion, and a limited DNA repair repertoire.FEMS yeast research · 2025Article
- VdAHA1 positively regulate pathogenicity inFrontiers in microbiology · 2025Article
- Interdisciplinary approaches for the discovery of novel antifungals.Trends in molecular medicine · 2024Review
- Roles of Hsp90 in Candida albicans morphogenesis and virulence.Current opinion in microbiology · 2023Review
- Resolving the Temporal Splenic Proteome during Fungal Infection for Discovery of Putative Dual Perspective Biomarker Signatures.Journal of the American Society for Mass Spectrometry · 2023Article
- Insights and Perspectives on the Role of Proteostasis and Heat Shock Proteins in Fungal Infections.Microorganisms · 2023Review
- Complete genome analysis of pathogenic Metschnikowia bicuspidata strain MQ2101 isolated from diseased ridgetail white prawn, Exopalaemon carinicauda.BMC microbiology · 2023Article
- Genome-wide analysis of heat stress-stimulated transposon mobility in the human fungal pathogenProceedings of the National Academy of Sciences of the United States of America · 2023Article
- Transcriptome reveals the role of theFrontiers in microbiology · 2023Article
- Molecular mechanisms governing antifungal drug resistance.npj antimicrobials and resistance · 2023Review
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
The opportunistic human fungal pathogen Cryptococcus neoformans has tremendous impact on global health, causing 181,000 deaths annually. Current treatment options are limited, and the frequent development of drug resistance exacerbates the challenge of managing invasive cryptococcal infections. In diverse fungal pathogens, the essential molecular chaperone Hsp90 governs fungal survival, drug resistance, and virulence. Therefore, targeting this chaperone has emerged as a promising approach to combat fungal infections. However, the role of Hsp90 in supporting C. neoformans pathogenesis remains largely elusive due to a lack of genetic characterization. To help dissect the functions of Hsp90 in C. neoformans, we generated a conditional expression strain in which HSP90 is under control of the copper-repressible promoter CTR4-2. Addition of copper to culture medium depleted Hsp90 transcript and protein levels in this strain, resulting in compromised fungal growth at host temperature; increased sensitivity to stressors, including the azole class of antifungals; altered C. neoformans morphology; and impaired melanin production. Finally, leveraging the fact that copper concentrations vary widely in different mouse tissues, we demonstrated attenuated virulence for the CTR4-2p-HSP90 mutant specifically in an inhalation model of Cryptococcus infection. During invasion and establishment of infection in this mouse model, the pathogen is exposed to the relatively high copper concentrations found in the lung as compared to blood. Overall, this work generates a tractable genetic system to study the role of Hsp90 in supporting the pathogenicity of C. neoformans and provides proof-of-principle that targeting Hsp90 holds great promise as a strategy to control cryptococcal infection.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.