Candida (Candidozyma) auris strains exposed to azole fungicides become less susceptible to manogepix

Candida auris is a multidrug-resistant fungal pathogen responsible for invasive nosocomial infections with high mortality rates. Recent detection of C. auris in natural environments suggests the existence of an environmental reservoir, prompting investigation into the potential role of azole fungicides used for plant protection in the development of resistance to antifungals used in human medicine. Here, we assessed the impact of azole fungicides on in vitro resistance development in two C. auris strains (B11220 and B11221) through sequential exposure to epoxiconazole, propiconazole, or tebuconazole. Exposure resulted in a rapid and significant increase in fungicide MICs, accompanied by a reduced susceptibility to four azole antifungals (fluconazole, voriconazole, posaconazole, isavuconazole), and to a new antifungal agent, the manogepix. Several strains with elevated MICs exhibited stable phenotypes and were associated with a mutation in the TAC1B gene. One of these strains showed a significant overexpression of the efflux pump CDR1. These findings provide experimental evidence that azole fungicides can drive resistance to azole antifungals and reduce susceptibility to manogepix, underscoring the need for integrated One Health antifungal stewardship strategies to combat C. auris.