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Mechanism of Fluconazole Resistance in Candida krusei
Open accessAbstract
The mechanisms of fluconazole resistance in three clinical isolates of Candida krusei were investigated. Analysis of sterols of organisms grown in the absence and presence of fluconazole demonstrated that the predominant sterol of C. krusei is ergosterol and that fluconazole inhibits 14alpha-demethylase in this organism. The 14alpha-demethylase activity in cell extracts of C. krusei was 16- to 46-fold more resistant to inhibition by fluconazole than was 14alpha-demethylase activity in cell extracts of two fluconazole-susceptible strains of Candida albicans. Comparing the carbon monoxide difference spectra of microsomes from C. krusei with those of microsomes from C. albicans indicated that the total cytochrome P-450 content of C. krusei is similar to that of C. albicans. The Soret absorption maximum in these spectra was located at 448 nm for C. krusei and at 450 nm for C. albicans. Finally, the fluconazole accumulation of two of the C. krusei isolates was similar to if not greater than that of C. albicans. Thus, there are significant qualitative differences between the 14alpha-demethylase of C. albicans and C. krusei. In addition, fluconazole resistance in these strains of C. krusei appears to be mediated predominantly by a reduced susceptibility of 14alpha-demethylase to inhibition by this drug.
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“The main mechanism of resistance to azoles in C. krusei appears to be the reduced susceptibility of 14α-demethylase to fluconazole [92].”
From Evolutionary Emergence of Drug Resistance in Candida Opportunistic Pathogens (2018) · cites this paper as [92]
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Metadata
- Authors
- Orozco, A. S., Higginbotham, L. M., Hitchcock, C. A., Parkinson, T., Falconer, D., Ibrahim, A. S., Ghannoum, M. A., & Filler, S. G.
- Affiliations
- University of California, Los Angeles (US)
- Pfizer (United Kingdom) (GB)
- Venue
- Antimicrobial Agents and Chemotherapy
- Publisher
- American Society for Microbiology
- Published
- 1998-10
- Volume
- 42
- Issue
- 10
- Pages
- 2645-2649
- ISSN
- 0066-4804 (ISSN-L)
- 1098-6596
- PMC
- PMC105912
- OpenAlex
- W2122676815
- Cited by
- 218
- References
- 34
- Citations by year
- 2026: 10 · 2025: 4 · 2024: 6 · 2023: 4 · 2022: 7 · 2021: 12 · 2020: 18 · 2019: 7 · 2018: 6 · 2017: 9 · 2016: 14 · 2015: 14 · 2014: 6 · 2013: 7 · 2012: 5
- FWCI
- 3.28
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Antimicrobial Agents and Chemotherapy (publishedVersion)
- PubMed Central (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Georgetown University
- Topics
- Health Sciences › Medicine › Infectious Diseases › Antifungal resistance and susceptibility
- Life Sciences › Agricultural and Biological Sciences › Plant Science › Fungal Plant Pathogen Control
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
- Keywords
- fluconazole resistance, Candida krusei, Candida albicans, 14α-demethylase, ergosterol, sterol composition, cytochrome P450
- MeSH terms
- Antifungal Agents, Candida, Cytochrome P-450 Enzyme System, Drug Resistance, Microbial, Ergosterol, Oxidoreductases, Fluconazole, Sterol 14-Demethylase, Cytochrome P-450 Enzyme Inhibitors
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