Antifungal

Antifungal drug

Gene

Cell biology

Biology

Heat shock protein

Corpus albicans

Drug resistance

Azole

Biochemistry

Botany

Ergosterol

Candida auris

Genetics

Candida albicans

Microbiology

Hsp90

Virulence

Efflux

mBio

Fungal pathogens pose a serious threat to public health. Candida auris is an emerging fungal pathogen that is often resistant to commonly used antifungal drugs. However, the mechanisms governing drug resistance and virulence in this organism remain largely unexplored. In this study, we adapted a conditional expression system to modulate the transcription of an essential gene, HSP90 , which regulates antifungal resistance and virulence in diverse fungal pathogens. We showed that Hsp90 is essential for growth in C. auris and is important for tolerance of the clinically important azole antifungals, which block ergosterol biosynthesis. Further, we established that the Cdr1 efflux transporter regulates azole resistance. Finally, we discovered that C. auris transitions from yeast to filamentous growth in response to Hsp90 inhibition, accompanied by global transcriptional remodeling. Overall, this work provides a novel insight into mechanisms regulating azole resistance in C. auris and uncovers a distinct developmental program regulated by Hsp90.

Genetic Analysis of <i>Candida auris</i> Implicates Hsp90 in Morphogenesis and Azole Tolerance and Cdr1 in Azole Resistance

Genetic Analysis of Candida auris Implicates Hsp90 in Morphogenesis and Azole Tolerance and Cdr1 in Azole Resistance