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Hsp90 Orchestrates Stress Response Signaling Governing Fungal Drug Resistance
Open accessAbstract
The emergence of drug resistance in microbial pathogens provides a poignant example of an evolutionary process with a profound impact on human health.Fungal drug resistance poses a particular concern given the limited number of clinically useful antifungal drugs and the growing population of immunocompromised individuals vulnerable to life-threatening fungal disease [1].The efficacy of most antifungal drugs is compromised either by host toxicity, fungistatic rather than fungicidal activity, or by the emergence of drug resistance.Recent studies have revealed that compromising the function of the molecular chaperone Hsp90 can render resistant pathogens more responsive to treatment and can thwart the evolution of fungal drug resistance [2].
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“has been shown to potentiate the evolution of drug resistance traits, including some azole resistance mechanisms.”
From Molecular and genetic basis of azole antifungal resistance in the opportunistic pathogenic fungus Candida albicans (2020) · cites this paper as [167]
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“by stabilizing the calcineurin protein and the pathway that is essential in the cellular drug-induced stress response, Hsp90 has been shown to affect not only azole resistance but resistance to the echinocandin drug class as well.”
From Molecular and genetic basis of azole antifungal resistance in the opportunistic pathogenic fungus Candida albicans (2020) · cites this paper as [167]
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“there is increasing evidence of its regulatory role in azole resistance development.”
From Molecular and genetic basis of azole antifungal resistance in the opportunistic pathogenic fungus Candida albicans (2020) · cites this paper as [167]
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Cites
HSP90 and the chaperoning of cancer
Whitesell, L., & Lindquist, S. L. (2005) · Nature Reviews Cancer · doi:10.1038/nrc1716 · Cited by 2,502
Hsp90 as a capacitor for morphological evolution
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Self-citationHsp90 Governs Echinocandin Resistance in the Pathogenic Yeast Candida albicans via Calcineurin
Singh, S. D., Robbins, N., Zaas, A. K., Schell, W. A., Perfect, J. R., & Cowen, L. E. (2009) · PLoS Pathogens · doi:10.1371/journal.ppat.1000532 · Cited by 362 · cited 1×
“clinical isolates and creates a fungicidal combination”
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Calcineurin signaling in Saccharomyces cerevisiae: how yeast go crazy in response to stress.
Cyert, M. S. (2003) · Biochemical and Biophysical Research Communications · doi:10.1016/s0006-291x(03)01552-3 · Cited by 333
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Genome-Wide DNA Changes Acquired by Candida albicans Caspofungin-Adapted Mutants
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Mechanisms Of Dermatophyte Resistance To Antifungal Substances
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RetractedYeast Biofilms in the Context of Human Health and Disease
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Self-citationHuman Fungal Pathogens and Drug Resistance Against Azole Drugs
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Mechanisms of Resistance to Antifungal Agents
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Emerging Antifungal Resistance in Ocular Infections
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Metadata
- Authors
- Cowen, L. E.
- Affiliations
- University of Toronto (CA)
- Corresponding author
- Cowen, Leah E.
- ORCID
- Cowen, Leah E.
- Venue
- PLoS Pathogens
- Publisher
- Public Library of Science (PLoS)
- Published
- 2009-08-28
- Volume
- 5
- Issue
- 8
- Pages
- e1000471
- ISSN
- 1553-7366 (ISSN-L)
- 1553-7374
- PMC
- PMC2726949
- OpenAlex
- W2022326366
- Cited by
- 130
- References
- 21
- Citations by year
- 2026: 4 · 2025: 6 · 2024: 3 · 2023: 9 · 2022: 4 · 2021: 7 · 2020: 5 · 2019: 11 · 2018: 6 · 2017: 11 · 2016: 8 · 2015: 9 · 2014: 12 · 2013: 10 · 2012: 8
- FWCI
- 3.35
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- PLoS Pathogens (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Canadian Institutes of Health Research
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Heat shock proteins research
- Health Sciences › Medicine › Infectious Diseases › Antifungal resistance and susceptibility
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
- Keywords
- HSP90, molecular chaperones, fungal drug resistance, antifungal agents, stress signaling, immunocompromised patients, fungal pathogens, drug resistance evolution
- MeSH terms
- Antifungal Agents, Aspergillus fumigatus, Azoles, Candida albicans, Phenotype, Signal Transduction, HSP90 Heat-Shock Proteins, Calcineurin, Drug Resistance, Fungal, Echinocandins
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