title: Novel point mutations in the ERG11 gene in clinical isolates of azole resistant Candida species.
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 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.
authors.affiliation: Universidade Federal da Grande Dourados, Dourados, MS, Brasil.
authors.forename: Danielly Beraldo dos Santos
authors.initials: DB
authors.lastname: Silva
authors.affiliation: Universidade Federal da Grande Dourados, Dourados, MS, Brasil.
authors.forename: Luana Mireli Carbonera
authors.initials: LM
authors.lastname: Rodrigues
authors.affiliation: Universidade Federal de Mato Grosso do Sul, Campo Grande, MS, Brasil.
authors.forename: Adriana Araújo de
authors.initials: AA
authors.lastname: Almeida
authors.affiliation: Universidade Federal da Grande Dourados, Dourados, MS, Brasil.
authors.forename: Kelly Mari Pires de
authors.initials: KM
authors.lastname: Oliveira
authors.affiliation: Universidade Federal da Grande Dourados, Dourados, MS, Brasil.
authors.forename: Alexéia Barufatti
authors.initials: AB
authors.lastname: Grisolia
mesh_terms: D000935:Antifungal Agents / Q000494:pharmacology; D001393:Azoles / Q000494:pharmacology; D002175:Candida / Q000145:classification / Q000187:drug effects* / Q000235:genetics* / Q000302:isolation & purification; D041221:Candida glabrata / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D025141:Drug Resistance, Fungal / Q000235:genetics*; D005800:Genes, Fungal; D006239:Haplotypes / Q000187:drug effects; D006801:Humans; D008826:Microbial Sensitivity Tests; D010802:Phylogeny; D017354:Point Mutation / Q000187:drug effects*; D058886:Sterol 14-Demethylase / Q000235:genetics*; D065819:Voriconazole / Q000494:pharmacology
chemical_list: D000935:Antifungal Agents; D001393:Azoles; D058886:Sterol 14-Demethylase; D065819:Voriconazole