Erg11 mutations associated with azole resistance in clinical isolates of Candida albicans.
FEMS Yeast Res
; 13(4): 386-93, 2013 Jun.
Article
en 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
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Azoles
/
Candida albicans
/
Mutación Missense
/
Sistema Enzimático del Citocromo P-450
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Farmacorresistencia Fúngica
/
Antifúngicos
Tipo de estudio:
Risk_factors_studies
Límite:
Humans
Idioma:
En
Revista:
FEMS Yeast Res
Asunto de la revista:
MICROBIOLOGIA
Año:
2013
Tipo del documento:
Article
País de afiliación:
China