Erg11 mutations associated with azole resistance in clinical isolates of Candida albicans.
FEMS Yeast Res
; 13(4): 386-93, 2013 Jun.
Article
em En
| MEDLINE
| ID: mdl-23480635
ABSTRACT
The widespread use of azoles has led to increasing azole resistance among Candida albicans strains. One mechanism of azole resistance involves point mutations in the ERG11 gene, which encodes the target enzyme (cytochrome P450 lanosterol 14α-demethylase). In the present study, we amplified and sequenced the ERG11 gene of 23 C. albicans clinical isolates. Seventeen mutations encoding distinct amino acid substitutions were found, of which seven (K143Q, Y205E, A255V, E260V, N435V, G472R, and D502E) were novel. We further verified the contribution of the amino acid substitutions to azole resistance using site-directed mutagenesis of the ERG11 gene to recreate these mutations for heterologous expression in Saccharomyces cerevisiae. We observed that substitutions A114S, Y132H, Y132F, K143R, Y257H, and a new K143Q substitution contributed to significant increases (â§fourfold) in fluconazole and voriconazole resistance; changes in itraconazole resistance were not significant (â¦twofold).
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Azóis
/
Candida albicans
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Mutação de Sentido Incorreto
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Sistema Enzimático do Citocromo P-450
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Farmacorresistência Fúngica
/
Antifúngicos
Tipo de estudo:
Risk_factors_studies
Limite:
Humans
Idioma:
En
Revista:
FEMS Yeast Res
Assunto da revista:
MICROBIOLOGIA
Ano de publicação:
2013
Tipo de documento:
Article
País de afiliação:
China