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Candida albicans  cells homozygous at the mating-type locus stochastically undergo the white-to-opaque switching to become mating-competent. This switching is regulated by a core circuit of transcription factors organized through interlocking feedback loops around the master regulator Wor1. Although a range of distinct environmental cues is known to induce the switching, the pathways linking the external stimuli to the central control mechanism remains largely unknown. By screening a  C. albicans  haploid gene-deletion library, we found that  SAC7  encoding a GTPase-activating protein of Rho1 is required for the white-to-opaque switching. We demonstrate that Sac7 physically associates with Rho1-GTP and the constitutively active Rho1 G18V  mutant impairs the white-to-opaque switching while the inactive Rho1 D124A  mutant promotes it. Overexpressing  WOR1  in both  sac7Δ/Δ  and  rho1   G18V   cells suppresses the switching defect, indicating that the Sac7/Rho1 module acts upstream of Wor1. Furthermore, we provide evidence that Sac7/Rho1 functions in a pathway independent of the Ras/cAMP pathway which has previously been positioned upstream of Wor1. Taken together, we have discovered new regulators and a signaling pathway that regulate the white-to-opaque switching in the most prevalent human fungal pathogen  C. albicans .

Sac7 and Rho1 regulate the white-to-opaque switching in Candida albicans