ABSTRACTCandida albicansis a commensal in heathy people but has the potential to become an opportunistic pathogen and is responsible for half of all clinical infections in immunocompromised patients. Central to understandingC. albicansbehavior is the white-opaque phenotypic switch, in which cells can undergo an epigenetic transition between the white state and the opaque state. The phenotypic switch regulates multiple properties, including biofilm formation, virulence, mating, and fungus-host interactions. Switching between the white and opaque states is associated with many external stimuli, such as oxidative stress, pH, andN-acetylglucosamine, and is directly regulated by the Wor1 transcriptional circuit. The Hog1 stress-activated protein kinase (SAPK) pathway is recognized as the main pathway for adapting to environmental stress inC. albicans. In this work, we first show that loss of theHOG1gene ina/aand α/α cells, but nota/α cells, results in 100% white-to-opaque switching when cells are grown on synthetic medium, indicating that switching is repressed by thea1/α2 heterodimer that repressesWOR1gene expression. Indeed, switching in thehog1Δ strain was dependent on the presence ofWOR1, as ahog1Δwor1Δ strain did not show switching to the opaque state. Deletion ofPBS2andSSK2also resulted inC. albicanscells switching from white to opaque with 100% efficiency, indicating that the entire Hog1 SAPK pathway is involved in regulating this unique phenotypic transition. Interestingly, all Hog1 pathway mutants also caused defects in shmoo formation and mating efficiencies. Overall, this work reveals a novel role for the Hog1 SAPK pathway in regulating white-opaque switching and sexual behavior inC. albicans.
Negative control of Candida albicans filamentation-associated gene expression by essential protein kinase gene KIN28