The antimicrobial photodynamic inactivation resistance of Candida albicans is modulated by the Hog1 pathway and the Cap1 transcription factor.

Candida albicans is the most important fungal pathogen afflicting humans, particularly immunocompromised patients. However, currently available antifungal drugs are limited and ineffective against drug-resistant strains. The development of new drugs or alternative therapeutic approaches to control fungal infections is urgent and necessary. Photodynamic inactivation (PDI) is a new promising therapy for eradicating microorganism infections through combining visible light, photosensitizers, and oxygen to generate reactive oxygen species (ROS). Although cytoprotective responses induced by photodynamic therapy (PDT) have been well studied in cancer cells, the mechanisms by which C. albicans responds to PDI are largely unknown. In this study, we first demonstrated that PDI induces C. albicans Hog1p activation. Deletion of any of the SSK2, PBS2, and HOG1 genes significantly decreased the survival rate after photochemical reactions, indicating that the Hog1 SAPK pathway is required for tolerance to PDI. Furthermore, the basic leucine zipper transcription factor Cap1 that regulates several downstream antioxidant genes was highly expressed during the response to PDI, and loss of CAP1 also resulted in decreased C. albicans survival rates. This study demonstrates the importance of the Hog1 SAPK and the Cap1 transcription factor, which regulates in resistance to PDI-mediated oxidative stress in C. albicans. Understanding the mechanisms by which C. albicans responds to PDI and consequently scavenges ROS will be very useful for the further development of therapeutics to control fungal infectious diseases, particularly those of the skin and mucosal infections.