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

The azoles are the class of medications most commonly used to fight infections causedby Candida sp. Typically, resistance can be attributed to mutationsin ERG11 gene (CYP51) which encodes the cytochrome P45014α-demethylase, the primary target for the activity of azoles. The objective of thisstudy was to identify mutations in the coding region of theERG11gene in clinical isolates of Candidaspecies known to be resistant toazoles. We identified three new synonymous mutations in the ERG11gene in the isolates of Candida glabrata (C108G, C423T and A1581G)and two new nonsynonymous mutations in the isolates of Candidakrusei - A497C (Y166S) and G1570A (G524R). The functional consequence ofthese nonsynonymous mutations was predicted using evolutionary conservation scores.The G524R mutation did not have effect on 14α-demethylase functionality, while theY166S mutation was found to affect the enzyme. This observation suggests a possiblelink between the mutation and dose-dependent sensitivity to voriconazole in theclinical isolate of C. krusei. Although the presence of the Y166S inphenotype of reduced azole sensitivity observed in isolate C.kruseidemands investigation, it might contribute to the search of newtherapeutic agents against resistant Candida isolates.