Novel point mutations in the ERG11 gene in clinical isolates of azole resistant Candida species

摘要

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 P45014α-demethylase, the primary target for the activity of azoles. The objective of this study was to identify mutationsin the coding region of the ERG11 gene in clinical isolates of Candida known to be resistant to azoles. Weidentified three new synonymous mutations in the ERG11 gene in the isolates of Candida glabrata (C108G, C423Tand 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 conservationscores. The G524R mutation did not have effect on 14α-demethylase functionality, while the Y166S mutationwas found to affect the enzyme. This observation suggests a possible link between the mutation and dose-dependentsensitivity to voriconazole in the clinical isolate of C. krusei. Although the presence of the Y166S in phenotype ofreduced azole sensitivity observed in isolate C. krusei demands investigation, it might contribute to the search ofnew therapeutic agents against resistant Candida isolates.