Functional genomic analysis of Candida albicans protein kinases reveals modulators of morphogenesis in diverse environments

Candida albicans is a leading cause of mycotic infection. The ability to transition between yeast and filamentous forms is critical to C. albicans virulence and complex signaling pathways regulate this process. Here, we screened a C. albicans protein kinase mutant library in six environmental conditions to identify regulators of morphogenesis. We identified the uncharacterized gene orf19.3751 as a negative regulator of filamentation and follow-up investigations implicated a role for orf19.3751 in cell cycle regulation. We also uncovered a dual role for the kinases Ire1 and protein kinase A (Tpk1 and Tpk2) in C. albicans morphogenesis, specifically as negative regulators of wrinkly colony formation on solid medium but positive regulators of filamentation in liquid medium. Further analyses suggested Ire1 modulates morphogenesis in both media states in part through the transcription factor Hac1 and in part through independent mechanisms. Overall, this work provides insights into the signaling governing morphogenesis in C. albicans.