Novel point mutations in the ERG11 gene in clinical isolates of azole resistant Candida species

Silva, Danielly Beraldo dos Santos; Rodrigues, Luana Mireli Carbonera; Almeida, Adriana Araújo de; Oliveira, Kelly Mari Pires de; Grisolia/, Alexéia Barufatti

doi:10.1590/0074-02760150400

Cited by 42Antifungal resistance and susceptibilityFungal Plant Pathogen ControlFungal and yeast genetics research

Novel point mutations in the ERG11 gene in clinical isolates of azole resistant Candida species

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Silva, Danielly Beraldo dos Santos, Rodrigues, Luana Mireli Carbonera, Almeida, Adriana Araújo de, Oliveira, Kelly Mari Pires de, Grisolia/, Alexéia Barufatti·2016·Memórias do Instituto Oswaldo Cruz

DOI 10.1590/0074-02760150400PMC PMC4804502

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Abstract

The azoles are the class of medications most commonly used to fight infections caused by Candida sp. Typically, resistance can be attributed to mutations in ERG11 gene (CYP51) which encodes the cytochrome P450 14α-demethylase, the primary target for the activity of azoles. The objective of this study was to identify mutations in the coding region of theERG11 gene in clinical isolates of Candida species known to be resistant to azoles. We identified three new synonymous mutations in the ERG11 gene in the isolates of Candida glabrata (C108G, C423T and A1581G) and two new nonsynonymous mutations in the isolates of Candida krusei--A497C (Y166S) and G1570A (G524R). The functional consequence of these nonsynonymous mutations was predicted using evolutionary conservation scores. The G524R mutation did not have effect on 14α-demethylase functionality, while the Y166S mutation was found to affect the enzyme. This observation suggests a possible link between the mutation and dose-dependent sensitivity to voriconazole in the clinical isolate of C. krusei. Although the presence of the Y166S in phenotype of reduced azole sensitivity observed in isolate C. krusei demands investigation, it might contribute to the search of new therapeutic agents against resistant Candida isolates.

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Reduced susceptibility to other types of azoles in C. krusei has been linked to point mutations in ERG11.
“In addition, reduced susceptibility to other types of azoles has also been linked to point mutations in ERG11 [95].”
From Evolutionary Emergence of Drug Resistance in Candida Opportunistic Pathogens (2018) · cites this paper as [95]

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Authors: Silva, D. B. D. S., Rodrigues, L. M. C., Almeida, A. A. D., Oliveira, K. M. P. D., & Grisolia/, A. B.
Affiliations: Universidade Federal da Grande Dourados (BR)
Universidade Federal de Mato Grosso do Sul, Brasil
Universidade Federal da Grande Dourados, Brasil
ORCID: Silva, Danielly Beraldo dos Santos
Oliveira, Kelly Mari Pires de
Venue: Memórias do Instituto Oswaldo Cruz
Publisher: FapUNIFESP (SciELO)
Published: 2016-03-15
Volume: 111
Issue: 3
Pages: 192-199
ISSN: 0074-0276 (ISSN-L)
1678-8060
DOI: 10.1590/0074-02760150400
PMC: PMC4804502
OpenAlex: W2297614255
Cited by: 42
References: 42
Citations by year: 2026: 1 · 2025: 3 · 2024: 6 · 2023: 7 · 2022: 5 · 2021: 3 · 2020: 5 · 2019: 6 · 2018: 3 · 2017: 2 · 2016: 1
FWCI: 3.69
Type: journal article
Language: en
Open access: diamond
doi.org
Licence: cc-by
Locations: Memórias do Instituto Oswaldo Cruz (publishedVersion, cc-by)
PubMed Central (publishedVersion, cc-by)
PubMed (publishedVersion)
LA Referencia (Red Federada de Repositorios Institucionales de Publicaciones Científicas) (publishedVersion, other-oa)
Bioline International (Bioline International) (submittedVersion)
Americanae (AECID Library) (submittedVersion, other-oa)
DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
Funders: Coordenação de Aperfeiçoamento de Pessoal de Nível Superior
Fundação de Apoio ao Desenvolvimento do Ensino, Ciência e Tecnologia do Estado de Mato Grosso do Sul
Topics: Health Sciences › Medicine › Infectious Diseases › Antifungal resistance and susceptibility
Life Sciences › Agricultural and Biological Sciences › Ecology, Evolution, Behavior and Systematics › Fungal Plant Pathogen Control
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
Keywords: ERG11, CYP51, azole resistance, Candida glabrata, Candida krusei, synonymous mutations, non-synonymous mutations, voriconazole, antifungal resistance, clinical isolates, enzyme function
MeSH terms: Antifungal Agents, Azoles, Candida, Dose-Response Relationship, Drug, Genes, Fungal, Haplotypes, Humans, Microbial Sensitivity Tests, Phylogeny, Point Mutation, Drug Resistance, Fungal, Candida glabrata, Sterol 14-Demethylase, Voriconazole

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Novel point mutations in the ERG11 gene in clinical isolates of azole resistant Candida species

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