Abrogation of triazole resistance upon deletion of CDR1 in a clinical isolate of Candida auris [Mechanisms of Resistance]

Candida auris has rapidly emerged as a healthcare-associated and multidrug-resistant pathogen of global concern. In this work, we examined the relative expression of the four C. auris genes with the highest degree of homology to C. albicans CDR1 and MDR1 among three triazole-resistant clinical isolates, as compared to the triazole-susceptible genome reference clinical isolate. We subsequently utilized a novel Cas9-mediated system for genetic manipulations to delete C. auris CDR1 and MDR1 in both a triazole-resistant clinical isolate and the susceptible reference strain, and observed MIC for all clinically available triazoles decreased as much as 128-fold in the CDR1 deletion strains. The findings of this work reveal for the first time that both C. auris CDR1 and MDR1 are more highly expressed among triazole-resistant clinical isolates of C. auris, and that the overexpression of CDR1 is a significant contributor to clinical triazole resistance.

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