The DOI matches its Crossref record; 21 of the 21 references it cites were found in a registry or an index.
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]
In the citing paper
“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]
In the citing paper
“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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Citations
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
Rutherford, S. L., & Lindquist, S. (1998) · Nature · doi:10.1038/24550 · Cited by 2,270
Hsp90 as a capacitor of phenotypic variation
Queitsch, C., Sangster, T. A., & Lindquist, S. (2002) · Nature · doi:10.1038/nature749 · Cited by 1,372
Zhao, R., Davey, M., Hsu, Y.-C., Kaplanek, P., Tong, A., Parsons, A. B., Krogan, N., Cagney, G., Mai, D., Greenblatt, J., et al. (2005) · Cell · doi:10.1016/j.cell.2004.12.024 · Cited by 819
Hsp90 Potentiates the Rapid Evolution of New Traits: Drug Resistance in Diverse Fungi
Cowen, L. E., & Lindquist, S. (2005) · Science · doi:10.1126/science.1118370 · Cited by 698
Self-citationCowen, L. E., Singh, S. D., Köhler, J. R., Collins, C., Zaas, A. K., Schell, W. A., Aziz, H., Mylonakis, E., Perfect, J. R., Whitesell, L., et al. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0813394106 · Cited by 413
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”
Self-citationSanglard, D., Ischer, F., Marchetti, O., Entenza, J., & Bille, J. (2003) · Molecular Microbiology · doi:10.1046/j.1365-2958.2003.03495.x · Cited by 350
Calcineurin is essential for survival during membrane stress in Candida albicans
Cruz, M. C., Goldstein, A. L., Blankenship, J. R., Del Poeta, M., Davis, D., Cardenas, M. E., Perfect, J. R., McCusker, J. H., & Heitman, J. (2002) · The EMBO Journal · doi:10.1093/emboj/21.4.546 · Cited by 342
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
Harnessing calcineurin as a novel anti-infective agent against invasive fungal infections.
Steinbach, W. J., Reedy, J. L., Cramer, R. A., Perfect, J. R., & Heitman, J. (2007) · Nature Reviews Microbiology · doi:10.1038/nrmicro1680 · Cited by 313
Hsp90 Orchestrates Temperature-Dependent Candida albicans Morphogenesis via Ras1-PKA Signaling
Shapiro, R. S., Uppuluri, P., Zaas, A. K., Collins, C., Senn, H., Perfect, J. R., Heitman, J., & Cowen, L. E. (2009) · Current Biology · doi:10.1016/j.cub.2009.03.017 · Cited by 311
Self-citationThe evolution of fungal drug resistance: modulating the trajectory from genotype to phenotype.
Cowen, L. E. (2008) · Nature Reviews Microbiology · doi:10.1038/nrmicro1835 · Cited by 311
Self-citationPachl, J., Svoboda, P., Jacobs, F., Vandewoude, K., van der Hoven, B., Spronk, P., Masterson, G., Malbrain, M., Aoun, M., Garbino, J., et al. (2006) · Clinical Infectious Diseases · doi:10.1086/503428 · Cited by 307
Stress, drugs, and evolution: the role of cellular signaling in fungal drug resistance.
Cowen, L. E., & Steinbach, W. J. (2008) · Eukaryotic Cell · doi:10.1128/ec.00041-08 · Cited by 285
Self-citationGenetic Architecture of Hsp90-Dependent Drug Resistance
Cowen, L. E., Carpenter, A. E., Matangkasombut, O., Fink, G. R., & Lindquist, S. (2006) · Eukaryotic Cell · doi:10.1128/ec.00274-06 · Cited by 159
Self-citationRole of HSP90 in salt stress tolerance via stabilization and regulation of calcineurin.
Imai, J., & Yahara, I. (2000) · Molecular and Cellular Biology · doi:10.1128/mcb.20.24.9262-9270.2000 · Cited by 123
Onyewu, C., Wormley, F. L., Perfect, J. R., & Heitman, J. (2004) · Infection and Immunity · doi:10.1128/iai.72.12.7330-7333.2004 · Cited by 121
Mylonakis, E. E. (2007) · Mycopathologia · doi:10.1007/s11046-007-9082-z · Cited by 109
Calcineurin Inhibition or Mutation Enhances Cell Wall Inhibitors against Aspergillus fumigatus
Steinbach, W. J., Cramer, R. A., Perfect, B. Z., Henn, C., Nielsen, K., Heitman, J., & Perfect, J. R. (2007) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.01394-06 · Cited by 108
Kumar, R., Musiyenko, A., & Barik, S. (2005) · Molecular and Biochemical Parasitology · doi:10.1016/j.molbiopara.2005.01.012 · Cited by 71
Cited by
Sorted by citations
The Response to Heat Shock and Oxidative Stress in Saccharomyces cerevisiae
Morano, K. A., Grant, C. M., & Moye-Rowley, S. (2011) · Genetics · doi:10.1534/genetics.111.128033 · Cited by 674
Drug resistance and tolerance in fungi.
Berman, J., & Krysan, D. J. (2020) · Nature Reviews Microbiology · doi:10.1038/s41579-019-0322-2 · Cited by 642
Mechanisms of Antifungal Drug Resistance
Cowen, L. E., Sanglard, D., Howard, S. J., Rogers, P. D., & Perlin, D. S. (2015) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a019752 · Cited by 647
Self-citationLaFayette, S. L., Collins, C., Zaas, A. K., Schell, W. A., Betancourt-Quiroz, M., Gunatilaka, A. A. L., Perfect, J. R., & Cowen, L. E. (2010) · PLoS Pathogens · doi:10.1371/journal.ppat.1001069 · Cited by 329
Self-citationMechanisms of echinocandin antifungal drug resistance
Perlin, D. S. (2015) · Annals of the New York Academy of Sciences · doi:10.1111/nyas.12831 · Cited by 313
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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