MOLECULAR CHARACTERIZATION OF ERG11 GENE IN TRIAZOLE RESISTANT CANDIDA ALBICANS ISOLATED FROM A TERTIARY CARE HOSPITAL

Abstract

Treatment options for Candidiasis include polyenes, azoles, echinocandins, nucleoside analogues, and allylamines, but drug resistance is a growing problem. Some species, like C. krusei and C. glabrata, exhibit high resistance to fluconazole and azoles. Accurate identification of Candida species and their susceptibility patterns is crucial for effective treatment. Mutations in the ERG11 gene, responsible for lanosterol 14α-demethylase enzyme production, lead to azole drug resistance, reducing their efficacy. This study focuses on identifying ERG11 gene mutations, offering prognostic and therapeutic significance in preventing drug resistance
emergence. The triazole resistant Candida albicans isolates were selected and the DNA is extracted. ERG11 gene is amplified and sequenced to find point mutations and the substituted amino acids by using ABI 3500 XL genetic analyzer. A total of 83 mutations in the ERG11 gene of 10 isolates of C. albicans which were resistant to Fluconazole, Voriconazole and Itraconazole were detected in this study. Of the 83 mutations, 56 mutations resulted in change in amino acid (missense mutations) and 27 were silent mutations
where the change in nucleotide sequence did not result in any change in the amino acid. D116E, E266D and G464S mutations occurred 6 times each in the 10 isolates. K128T, I147T mutations were found in 4 isolates. A114S, S405F, T229A, G465S, K143E mutations were found in 3 isolates. R467K, R523G, V488I, W520C mutations were found in 2 isolates. This study further establishes that the ERG11 gene point mutations are one of the major causes of azole antifungal drug resistance in Candida albicans.