S5.1d Mechanisms of azole antifungal resistance in clinical isolates of Candida tropicalis
Abstract
Abstract S5.1 Antifungal resistance, September 22, 2022, 3:00 PM - 4:30 PM Objectives In tropical countries, the azole resistance in Candida tropicalis is on the rise. There are limited studies available regarding the azole resistance mechanisms in C. tropicalis. This study was designed to understand the molecular mechanisms of azole resistance in C. tropicalis by using genetic and bioinformatics approaches. Methods A total of 32 azole-resistant (R) and 10 azole-susceptible (S) clinical isolates of C. tropicalis were included in this study. All the isolates were subjected to complete gene sequencing of azole target genes including ERG11 to analyze the mutations which could lead the azole resistance. Four fragments were amplified, sequenced, and aligned to get full-length ERG11 gene. 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. Results 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 <.05) than those with mutation (R-WM) and the sensitive isolates (3.2-11 vs. 0.2-2.5, and 0.3-2.2 folds, respectively). Although the R-WTM and R-WM had higher (P <.05) CDR2 and MRR1…
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