Modulation of fluconazole sensitivity by the interaction of mitochondria and Erg3p in Saccharomyces cerevisiae
Abstract
We studied the effects of fluconazole, an ergosterol-depleting agent, in Saccharomyces cerevisiae, a genetically tractable fungus closely related to Candida albicans. The wild-type Saccharomyces strain was sensitive to fluconazole, but the isogenic cytoplasmic petite mutant (rho-) was resistant. The mechanism of resistance of rho- mutants appeared to involve uncoupling of oxidative phosphorylation. However, the petite strain with a mutation in cent5, 6 desaturase (erg3 rho-) was sensitive to fluconazole, in contrast to its erg3 rho+ counterpart. It is known that erg3 mutants are azole resistant through the accumulation of 14-methyl-fecosterol, a less toxic ergosterol intermediate. These results indicate that mitochondria function as important physiological partners with Erg3p in the accumulation of toxic sterol intermediates in the presence of azoles.
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A relationship between mitochondria function, sterol homeostasis, and azole drug resistance has been observed in the yeast S. cerevisiae and Candida glabrata.
“Second, a relationship between mitochondria function, sterol homeostasis, and azole drug resistance has been observed in the yeast S. cerevisiae and Candida glabrata [60],[61].”
From A Sterol-Regulatory Element Binding Protein Is Required for Cell Polarity, Hypoxia Adaptation, Azole Drug Resistance, and Virulence in Aspergillus fumigatus (2008) · cites this paper as [61]
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Self-citation
- Authors
- Kontoyiannis, D. P.
- Affiliations
- The University of Texas MD Anderson Cancer Center (US)
- Corresponding author
- Kontoyiannis, D. P.
- Venue
- Journal of Antimicrobial Chemotherapy
- Publisher
- Oxford University Press (OUP)
- Published
- 2000-08-01
- Volume
- 46
- Issue
- 2
- Pages
- 191-197
- ISSN
- 0305-7453 (ISSN-L)
- 1460-2091
- OpenAlex
- W2100624226
- Cited by
- 70
- References
- 29
- Citations by year
- 2025: 1 · 2024: 1 · 2023: 8 · 2021: 2 · 2020: 1 · 2019: 1 · 2018: 2 · 2017: 2 · 2016: 2 · 2015: 1 · 2014: 2 · 2013: 2 · 2012: 3
- FWCI
- 3.38
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Antimicrobial Chemotherapy (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Pfizer
- Massachusetts General Hospital
- Massachusetts Institute of Technology
- National Cancer Institute (CA-16672, P30CA016672)
- Topics
- Health Sciences › Medicine › Infectious Diseases › Antifungal resistance and susceptibility
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Keywords
- fluconazole, azole resistance, Saccharomyces cerevisiae, petite mutants, mitochondrial uncoupling, oxidative phosphorylation, ergosterol biosynthesis, sterol intermediates, plasma membrane, Candida albicans
- MeSH terms
- Antifungal Agents, Culture Media, Drug Resistance, Microbial, Ergosterol, Microbial Sensitivity Tests, Mitochondria, Mutation, Oxidative Phosphorylation, Oxidoreductases, Saccharomyces cerevisiae, Sterols, Fluconazole
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