Unraveling the Calcineurin Pathway in Pan-Drug-Resistant Fungal Pathogen Candida auris

Unraveling the Calcineurin Pathway in Pan-Drug-Resistant Fungal Pathogen Candida auris

Hyunjin Cha, Ji-Seok Kim and Yong-Sun Bahn*

Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul, South Korea

*Email: ysbahn@yonsei.ac.kr

Candida auris is an emerging pan-drug-resistant fungal pathogen. Even though candidiasis exhibits high mortality rate as C. auris is resistant to multiple antifungal drugs, signaling pathways in C. auris are largely yet unknown. Therefore, we evaluated the pathobiological roles of the calcineurin pathway, which is known to be essential for virulence and drug resistance in other fungal pathogens, in C. auris. Calcineurin is a calcium and calmodulin-dependent serine/threonine protein phosphatase. Here, we showed that the catalytic subunit of calcineurin, CNA1, and the regulatory subunit of calcineurin, CNB1, have multiple roles in cell wall/membrane-damaging stress responses and antifungal drug resistance. Moreover, we observed that the knock-out mutant of CRZ1, a transcription factor of calcineurin, generally showed similar phenotypes as cna1Δ and cnb1Δ but at reduced severity. Additionally, we discovered that crz2Δ did not display the phenotypes related to the calcineurin pathway, indicating that Crz1, but not Crz2, is likely to be a transcription factor downstream of the calcineurin pathway. In conclusion, the calcineurin pathway plays pivotal roles in maintaining cell wall/membrane integrity and conferring resistance to various antifungal drugs in pan-drug-resistant C. auris.