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 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
(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.
