Cited by 107Antifungal resistance and susceptibilityFungal and yeast genetics researchFungal Plant Pathogen Control

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An A643V Amino Acid Substitution in Upc2p Contributes to Azole Resistance in Well-Characterized Clinical Isolates of Candida albicans

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Hoot, Samantha J., Smith, Adam R., Brown, Ryan P., White, Theodore C.·2011·Antimicrobial Agents and Chemotherapy

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Abstract

The Candida albicans Upc2p transcription factor regulates ERG11, encoding the target of azole drugs. Gain-of-function mutations that contribute to resistance were recently identified in a series of sequential clinical isolates (N. Dunkel, T. T. Liu, K. S. Barker, R. Homayouni, J. Morschhauser, and P. D. Rogers, Eukaryot. Cell 7:1180-1190, 2008). In the present study, UPC2 was sequenced from a matched set of 17 isolates. An A643V substitution was present in all of the isolates in the series that overexpressed ERG11. Azole susceptibility, ergosterol levels, and expression of ERG genes were elevated in the A643V clinical isolates and in reconstructed strains.

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“Previous studies show that activating mutations in Upc2 result in increased expression of ERG11 and decreased fluconazole susceptibility; however, only three substitutions (G648D, A643T, and A643V) in Upc2 have been identified in clinical isolates that contribute to azole resistance (7, 11, 12).”
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Authors: Hoot, S. J., Smith, A. R., Brown, R. P., & White, T. C.
Affiliations: Center for Infectious Disease Research (US)
Corresponding author: White, Theodore C.
ORCID: White, Theodore C.
Venue: Antimicrobial Agents and Chemotherapy
Publisher: American Society for Microbiology
Published: 2011-02
Volume: 55
Issue: 2
Pages: 940-942
ISSN: 0066-4804 (ISSN-L)
1098-6596
DOI: 10.1128/aac.00995-10
PMC: PMC3028767
OpenAlex: W1971071885
Cited by: 107
References: 24
Citations by year: 2026: 2 · 2025: 4 · 2024: 8 · 2023: 4 · 2022: 5 · 2021: 6 · 2020: 8 · 2019: 10 · 2018: 7 · 2017: 10 · 2016: 3 · 2015: 8 · 2014: 9 · 2013: 8 · 2012: 9
FWCI: 4.77
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: journals.asm.org/non-commercial-tdm-license (tdm)
Locations: Antimicrobial Agents and Chemotherapy (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: National Institutes of Health
National Institute of Dental and Craniofacial Research (R01DE011367, R01DE017078, R01 DE-11367, R01 DE 14161, R01DE014161)
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 › Plant Science › Fungal Plant Pathogen Control
Keywords: Candida albicans, azole resistance, ERG11, transcription factors, clinical isolates, ergosterol, antifungal resistance, gain-of-function mutations
MeSH terms: Antifungal Agents, Azoles, Candida albicans, Ergosterol, Fungal Proteins, Humans, Microbial Sensitivity Tests, Trans-Activators, Fluconazole, Gene Expression Regulation, Fungal, Sequence Analysis, DNA, Amino Acid Substitution, Drug Resistance, Fungal

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An A643V Amino Acid Substitution in Upc2p Contributes to Azole Resistance in Well-Characterized Clinical Isolates of Candida albicans

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