Novel point mutations in the ERG11 gene in clinical isolates of azole resistant Candida species.
Mem Inst Oswaldo Cruz
; 111(3): 192-9, 2016 Mar.
Article
en En
| MEDLINE
| ID: mdl-26982177
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.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Candida
/
Mutación Puntual
/
Farmacorresistencia Fúngica
/
Esterol 14-Desmetilasa
Tipo de estudio:
Prognostic_studies
Límite:
Humans
Idioma:
En
Revista:
Mem Inst Oswaldo Cruz
Año:
2016
Tipo del documento:
Article
País de afiliación:
Brasil
Pais de publicación:
Brasil