Project description:Candida auris clinical isolate FY279 was exposed to tebuconazole (32μg/ml). Randomly14 adaptors were chosen. 10 adaptors obtained resistance to tebuconazole. These resistant adaptors were sequenced.
Project description:Candida auris (Candidozyma auris) is a yeast pathogen that poses a public health threat because of its ability to develop antifungal resistance. Notably, most C. auris isolates are resistant to fluconazole. The efflux pump Cdr1 is a key contributor of azole resistance in C. auris. In C. albicans, Cdr1 is regulated by the transcription factor Tac1, which has two orthologs in C. auris (Tac1a and Tac1b). While the role of Tac1b has been described, little is known about Tac1a. In this study, we characterized the respective roles of Tac1a and Tac1b in azole resistance. To investigate their transcriptional regulation and binding targets, we performed RNA sequencing and ChEC-seq (Chromatin endogenous cleavage sequencing) for both transcription factors. RNA sequencing was carried out by comparing hyperactivated mutants (TAC1a-HA or TAC1b-HA) with the wild-type strain IV.1. ChEC-seq was performed in strains carrying endogenous C-terminal MNase fusions (TAC1a-MNase and TAC1b-MNase) and in a control strain expressing ectopically MNase (Free MNase). Both Tac1a and Tac1b mediate azole resistance in C. auris via regulation of Cdr1, with overlapping downstream targets and evidence of autoregulation.