Cited by 70Antifungal resistance and susceptibilityFungal and yeast genetics researchMitochondrial Function and Pathology

Modulation of fluconazole sensitivity by the interaction of mitochondria and Erg3p in Saccharomyces cerevisiae

Kontoyiannis, D. P.·2000·Journal of Antimicrobial Chemotherapy

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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Crossref · 10.1093/jac/46.2.191

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Authors
Kontoyiannis, D. P.
Affiliations
The University of Texas MD Anderson Cancer Center (US)
Corresponding author
Kontoyiannis, D. P.
Venue
Journal of Antimicrobial Chemotherapy
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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