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Author summary Rice blast disease, caused by Magnaporthe oryzae is a devastating disease of rice, causing major economic loss in rice production across the globe. Since its isolation in 1892, M. oryza...

Author summary The fungal pathogen Candida auris presents a global health threat due to its multidrug resistance and high mortality rates. Despite its clinical significance, the molecular mechanisms underlying its virulence and antifungal resistance remain poorly understood. This study investigates the complex role of the calcineurin signaling pathway in C. auris pathogenicity. Deletion of the calcineurin complex impairs extreme thermotolerance and compromises cell membrane and wall integrity, leading to increased susceptibility to azoles and echinocandins, antifungal agents targeting the cell membrane and wall, respectively. We also identified the Crz1 transcription factor as a downstream target of calcineurin signaling. Interestingly, unlike calcineurin mutants, Crz1 mutants are susceptible only to cell-membrane-targeting azoles but surprisingly exhibit increased resistance to cell-wall-targeting echinocandins, suggesting that the calcineurin pathway may regulate multiple transcription factors, including Crz1. Additionally, calcineurin was found to be essential for virulence in vivo, using two different animal infection models, Drosophila and mice. These findings highlight the essential role of the calcineurin pathway in C. auris virulence, offering novel insights into its role in antifungal resistance and virulence, and paving the way for targeted therapies.

Author summary A controlled interplay of networks that control gene expression and the intracellular transport of their respective regulators is essential for survival of multicellular organisms. The ...

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