Two Clinical Isolates of Candida glabrata Exhibiting Reduced Sensitivity to Amphotericin B Both Harbor Mutations in ERG2
Open accessAbstract
Two novel isolates of Candida glabrata exhibiting reduced sensitivity to amphotericin B (MIC, 8 μg ml(-1)) were found to be ERG2 mutants, wherein Δ(8)-sterol intermediates comprised >90% of the total cellular sterol fraction. Both harbored an alteration at Thr(121) in ERG2; the corresponding residue (Thr(119)) in Saccharomyces cerevisiae is essential for sterol Δ8-Δ7 isomerization. This constitutes the first report of C. glabrata harboring mutations in ERG2 and exhibiting reduced sensitivity to amphotericin B.
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Lower abundance of the enzyme has been observed in polyene-resistant species and attributed to mutations in ERG2, ERG3, ERG5, ERG6, and ERG11 genes.
“Lower abundance of the enzyme has been observed in polyene-resistant species, which has been attributed to mutations in ERG2 [61,112], ERG3 [51], ERG5 [60], ERG6 [113], and ERG11 [60] genes, which encode enzymes involved in ergosterol synthesis.”
From Evolutionary Emergence of Drug Resistance in Candida Opportunistic Pathogens (2018) · cites this paper as [112]
Excess amounts of ergosta-8-enol would be expected with impaired function of Erg2.
“Excess amounts of this sterol would be expected with impaired function of Erg2 ([27](#B27)).”
From Multidrug transporters and alterations in sterol biosynthesis contribute to azole antifungal resistance in Candida parapsilosis (2015) · cites this paper as [27]
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References 33 · Cited by 90
- Authors
- Hull, C. M., Bader, O., Parker, J. E., Weig, M., Gross, U., Warrilow, A. G. S., Kelly, D. E., & Kelly, S. L.
- Affiliations
- Swansea University (GB)
- Universitätsmedizin Göttingen (DE)
- ORCID
- Venue
- Antimicrobial Agents and Chemotherapy
- Publisher
- American Society for Microbiology
- Published
- 2012-12
- Volume
- 56
- Issue
- 12
- Pages
- 6417-6421
- ISSN
- 0066-4804 (ISSN-L)
- 1098-6596
- PMC
- PMC3497184
- OpenAlex
- W2161572958
- Cited by
- 90
- References
- 33
- Citations by year
- 2026: 4 · 2025: 11 · 2024: 11 · 2023: 9 · 2022: 7 · 2021: 6 · 2020: 11 · 2019: 2 · 2018: 7 · 2017: 7 · 2016: 1 · 2015: 6 · 2014: 5 · 2013: 3
- FWCI
- 3.09
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Antimicrobial Agents and Chemotherapy (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- GRO (submittedVersion)
- Funders
- Engineering and Physical Sciences Research Council
- 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
- Candida glabrata, amphotericin B resistance, ERG2, sterol intermediates, antifungal resistance, clinical isolates, sterol biosynthesis
- MeSH terms
- Amino Acid Sequence, Amphotericin B, Antifungal Agents, Azoles, Candidiasis, Fungal Proteins, Microbial Sensitivity Tests, Molecular Sequence Data, Mutation, Pyrimidines, Saccharomyces cerevisiae, Steroid Isomerases, Sterols, Triazoles, Fluconazole, Drug Resistance, Fungal, Candida glabrata, Voriconazole
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