Pharmacological targeting of Ire1 of Candida albicans

The common fungal pathogen Candida albicans primarily affects immunocompromised individuals and the rise in antifungal resistance underscores the urgent need for new treatment options. In this study, we investigate the potential of STF-83010, a human Ire1 inhibitor, as a treatment for candidiasis. Our findings reveal that STF-83010 effectively inhibits Hac1 splicing and increases susceptibility to DTT-induced ER stress. Additionally, the inhibitor significantly reduces biofilm formation and blocks the yeast-to-hyphal transition, two critical factors in C. albicans pathogenicity. Further analysis indicates that STF-83010 impairs thermotolerance and reduces the expression of virulence-related genes. Our findings suggest that STF-83010 can be used as an antifungal treatment to target the UPR pathway in C. albicans.