Linkage between genes involved in azole resistance and ergosterol biosynthesis
Open accessAbstract
Azole drugs act by blocking the biosynthesis of ergosterol, the sterol component of the fungal plasma membrane.Resistance to azole drugs appears frequently in fungi and can be typically acquired by changes in the coding sequence of the gene producing lanosterol 14α-demethylase, the azole target enzyme, or changes in the expression of this gene that is designated ERG11 [1].A second route of resistance involves increased expression of loci encoding ATPbinding cassette (ABC) transporters, which are thought to efflux drugs and prevent toxic intracellular concentrations from being achieved [2].These 2 resistance mechanisms have generally been considered to represent independent, unlinked modes of lowering azole susceptibility.Recent work in several different fungi support a different viewpoint: that these resistance modalities actually illuminate a physiological tie between the biosynthesis of ergosterol and expression of ABC transporter proteins.
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PDR1 encodes the central transcription factor that triggers expression of CDR1.
“Moreover, PDR1 encodes the central transcription factor that triggers the expression of CDR1 (Moye-Rowley, 2020).”
From Uncovering the connection between tunicamycin-induced respiratory deficiency and reduced fluconazole tolerance in Candida glabrata (2025) · cites this paper as Moye-Rowley, 2020
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References 20 · Cited by 29
- Authors
- Moye-Rowley, W. S.
- Venue
- PLoS Pathogens
- Publisher
- Public Library of Science (PLoS)
- Published
- 2020-09-03
- Volume
- 16
- Issue
- 9
- Pages
- e1008819
- ISSN
- 1553-7366 (ISSN-L)
- 1553-7374
- PMC
- PMC7470339
- OpenAlex
- W3083609144
- Cited by
- 29
- References
- 20
- Citations by year
- 2026: 1 · 2025: 9 · 2024: 5 · 2023: 3 · 2022: 8 · 2021: 3
- FWCI
- 0.46
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- 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
- National Institutes of Health
- National Institute of General Medical Sciences (R01GM049825)
- National Institute of Allergy and Infectious Diseases (R01AI152494, R21AI145316, R01AI143198)
- 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 › Agricultural and Biological Sciences › Ecology, Evolution, Behavior and Systematics › Fungal Plant Pathogen Control
- Keywords
- azole resistance, ergosterol biosynthesis, lanosterol 14α-demethylase, ERG11, ABC transporters, drug efflux, fungal drug resistance, genetic linkage
- MeSH terms
- Provitamins, Antifungal Agents, Azoles, Ergosterol, Fungi, Humans, Mycoses, Gene Expression Regulation, Fungal, Drug Resistance, Fungal, Gene Regulatory Networks
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