Deciphering the Tac1a / Tac1b network of azole resistance in Candidozyma auris
Candidozyma auris has become a pathogenic yeast of primary importance because of its ability to develop antifungal resistance and to cause nosocomial outbreaks of invasive candidiasis. Resistance to azoles (mainly fluconazole) is a hallmark of most C. auris clinical isolates and the efflux pump Cdr1 plays a key role in this process. The transcription factor Tac1b regulates CDR1 expression and its role in azole resistance has also been demonstrated. TAC1b is located on chromosome 5 in tandem with TAC1a, whose function is not yet elucidated. This study aimed at investigating the respective roles of Tac1a and Tac1b in azole resistance. TAC1b is known to acquire gain-of-function mutations that confer azole resistance, whereas no such mutations have been demonstrated for TAC1a. In this project, we performed in vitro microevolution under fluconazole stress using a strain in which TAC1b was replaced by TAC1a in order to force the evolution of TAC1a. The resulting azole-resistant cultures were retained, and both TAC1a alleles were amplified by PCR and subjected to short-read sequencing to detect potential TAC1a variants. However, no TAC1a mutations were detected.