期刊
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
卷 63, 期 4, 页码 -出版社
AMER SOC MICROBIOLOGY
DOI: 10.1128/AAC.00057-19
关键词
CDR1; Candida; Candida auris; antifungal resistance; drug efflux; efflux pumps; triazole
资金
- NIH NIAID [R01 A1058145]
Candida auris has rapidly emerged as a health care-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 Candida 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 a susceptible reference strain and observed that MICs 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 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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