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Memórias do Instituto Oswaldo Cruz
Fundação Oswaldo Cruz, Fiocruz
ISSN: 1678-8060
EISSN: 1678-8060
Vol. 111, No. 3, 2016, pp. 192-199
Bioline Code: oc16027
Full paper language: English
Document type: Research Article
Document available free of charge

Memórias do Instituto Oswaldo Cruz, Vol. 111, No. 3, 2016, pp. 192-199

 en Novel point mutations in the ERG11 gene in clinical isolates of azole resistant Candida check for this species in other resources species
Silva, Danielly Beraldo dos Santos; Rodrigues, Luana Mireli Carbonera; Almeida, Adriana Araújo de; Oliveira, Kelly Mari Pires de & Grisolia, Alexéia Barufatti

Abstract

The azoles are the class of medications most commonly used to fight infections caused by Candida check for this species in other resources 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 the ERG11 gene in clinical isolates of Candida known to be resistant to azoles. We identified three new synonymous mutations in the ERG11 gene in the isolates of Candida glabrata check for this species in other resources (C108G, C423T and A1581G) and two new nonsynonymous mutations in the isolates of Candida krusei check for this species in other resources - 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.

Keywords
yeasts; Candida krusei; voriconazole; 14α-demethylase; Y166S

 
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