Mechanisms of azole antifungal resistance in clinical isolates of Candida tropicalis

This study was designed to understand the molecular mechanisms of azole resistance in Candida tropicalis using genetic and bioinformatics approaches. Thirty-two azole-resistant and 10 azole-susceptible (S) clinical isolates of C. tropicalis were subjected to mutation analysis of the azole target genes including ERG11. Inducible expression analysis of 17 other genes potentially associated with azole resistance was also evaluated. Homology modeling and molecular docking analysis were performed to study the effect of amino acid alterations in mediating azole resistance. Of the 32 resistant isolates, 12 (37.5%) showed A395T and C461T mutations in the ERG11 gene. The mean overexpression of CDR1, CDR3, TAC1, ERG1, ERG2, ERG3, ERG11, UPC2, and MKC1 in resistant isolates without mutation (R-WTM) was significantly higher (p