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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.
Affiliation
  • Silva, Danielly Beraldo dos Santos; Universidade Federal da Grande Dourados. Dourados. BR
  • Rodrigues, Luana Mireli Carbonera; Universidade Federal da Grande Dourados. Dourados. BR
  • Almeida, Adriana Araújo de; Universidade Federal da Grande Dourados. Dourados. BR
  • Oliveira, Kelly Mari Pires de; Universidade Federal da Grande Dourados. Dourados. BR
  • Grisolia/, Alexéia Barufatti; Universidade Federal da Grande Dourados. Dourados. BR
Mem. Inst. Oswaldo Cruz ; 111(3): 192-199, Mar. 2016. tab, graf
Article in En | LILACS | ID: lil-777368
Responsible library: BR1.1
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 Candidaspecies 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. kruseidemands investigation, it might contribute to the search of new therapeutic agents against resistant Candida isolates.
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Full text: 1 Index: LILACS Main subject: Candida / Point Mutation / Drug Resistance, Fungal Type of study: Prognostic_studies Limits: Humans Language: En Journal: Mem. Inst. Oswaldo Cruz Journal subject: MEDICINA TROPICAL / PARASITOLOGIA Year: 2016 Type: Article

Full text: 1 Index: LILACS Main subject: Candida / Point Mutation / Drug Resistance, Fungal Type of study: Prognostic_studies Limits: Humans Language: En Journal: Mem. Inst. Oswaldo Cruz Journal subject: MEDICINA TROPICAL / PARASITOLOGIA Year: 2016 Type: Article