The A395T Mutation in ERG11 gene confers fluconazole resistance in Candida tropicalis causing candidemia
Abstract
The mechanism of fluconazole resistance in Candida tropicalis is still unclear. Recently, we isolated a fluconazole-resistant strain of C. tropicalis from the blood specimen of a patient with candidemia in China. In vitro antifungal susceptibility of the isolate was determined by using CLSI M27-A3 and E-test methods. The sequence of ERG11 gene was then analyzed, and the three-dimensional model of Erg11p encoded by ERG11 gene was also investigated. The sequencing of ERG11 gene revealed the mutation of A395T in this fluconazole-resistant isolate of C. tropicalis, resulting in the Y132F substitution in Erg11p. Sequence alignment and three-dimensional model comparison of Erg11ps showed high similarity between fluconazole-susceptible isolates of C. tropicalis and Candida albicans. The comparison of the three-dimensional models of Erg11ps demonstrated that the position of the Y132F substitution in this isolate of C. tropicalis is identical to the isolate of C. albicans with fluconazole resistance resulting from Y132F substitution in Erg11p. Hence, we ascertain that the Y132F substitution of Erg11p caused by A395T mutation in ERG11 gene confers the fluconazole resistance in C. tropicalis.
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For C. tropicalis, point mutation Y132F, overexpression, and deletion mutations in ERG11 have been described as causes for azole resistance.
“For C. tropicalis, point mutation (again Y132F) [89], overexpression [90], and deletion mutations in ERG11 [52] have been described as causes for azole resistance.”
From Evolutionary Emergence of Drug Resistance in Candida Opportunistic Pathogens (2018) · cites this paper as [89]
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References 34 · Cited by 36
- Authors
- Tan, J., Zhang, J., Chen, W., Sun, Y., Wan, Z., Li, R., & Liu, W.
- Affiliations
- Peking University (CN)
- Corresponding author
- Liu, Wei
- Venue
- Mycopathologia
- Published
- 2014-11-15
- Volume
- 179
- Issue
- 3-4
- Pages
- 213-218
- ISSN
- 0301-486X (ISSN-L)
- 1573-0832
- OpenAlex
- W2034450582
- Cited by
- 36
- References
- 34
- Citations by year
- 2026: 2 · 2025: 1 · 2024: 1 · 2023: 6 · 2022: 4 · 2021: 1 · 2020: 5 · 2019: 5 · 2018: 5 · 2017: 4 · 2016: 2
- FWCI
- 1.41
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Mycopathologia (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation of China
- Program for New Century Excellent Talents in University
- 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 tropicalis, candidemia, fluconazole resistance, ERG11, antifungal resistance, Candida albicans, protein 3D structure, antifungal susceptibility
- MeSH terms
- Antifungal Agents, Candidiasis, Cytochrome P-450 Enzyme System, Fungal Proteins, Humans, Fluconazole, Mutation, Missense, Candida tropicalis, Candidemia
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