Bistable expression of WOR1, a master regulator of white–opaque switching in Candida albicans

Candida albicans, a commensal organism and a pathogen of humans, can switch stochastically between a white phase and an opaque phase without an intermediate phase. The white and opaque phases have distinct cell shapes and gene expression programs. Once switched, each phase is stable for many cell divisions. White–opaque switching is under a1–α2 repression and therefore only happens in a or α cells. Mechanisms that control the switching are unknown. Here, we identify Wor1 (white–opaque regulator 1) as a master regulator of white–opaque switching. The deletion of WOR1 blocks opaque cell formation. The ectopic expression of WOR1 converts all cells to stable opaque cells in a or α cells. In addition, the ectopic expression of WOR1 in a/α cells is sufficient to induce opaque cell formation. Importantly, WOR1 expression displays an all-or-none pattern. It is undetectable in white cells, and it is highly expressed in opaque cells. The ectopic expression of Wor1 induces the transcription of WOR1 from the WOR1 locus, which correlates with the switch to opaque phase. We present genetic evidence for feedback regulation of WOR1 transcription. The feedback regulation explains the bistable and stochastic nature of white–opaque switching.