The PHO pathway regulates white-opaque switching and sexual mating in the human fungal pathogen Candida albicans.

The opportunistic fungal pathogen Candida albicans is able to switch among several morphological phenotypes in response to environmental changes. White-opaque transition is a typical phenotypic switching system involved in the regulation of pathogenesis and sexual reproduction in C. albicans. Under regular laboratory culture conditions, to undergo white-to-opaque switching, cells must first undergo homozygosis at the mating-type locus (MTLa/a or α/α) since the a1/α2 heterodimer represses the expression of the Wor1 master regulator of switching in MTLa/α heterozygous strains. In this study, we report the roles of the PHO pathway of phosphate metabolism in the regulation of white-opaque switching and sexual mating in C. albicans. We find that deletion of the PHO pathway genes PHO81, PHO80, PHO2, and PHO4 induces the opaque phenotype in MTLa/α heterozygous cells. Low concentrations of external phosphate are conducive for the opaque phenotype in both MTL homozygous and heterozygous strains. Moreover, phosphate starvation can also increase the mating efficiency in C. albicans. Consistently, the pho80/pho80 mutant mimics an artificial phosphate starvation state and mates efficiently at both lower and higher phosphate concentrations. Our study establishes a link between the PHO pathway and white-opaque epigenetic switching in C. albicans.