Deletion of EFG1 promotes Candida albicans opaque formation responding to pH via Rim101

Phenotypic switching in Candida albicans spontaneously generates different cellular morphologies. The reversible switching between white and opaque phenotypes is regulated by multiple regulators including Efg1 and Wor1. In mating-type-like locus (MTL) homozygous cells, the Efg1 functions as a repressor, whereas the Wor1 acts as an activator in white-opaque switching. We presented evidence that switching between white and opaque in efg1/efg1 mutant is regulated by ambient pH. In pH 6.8 media, the efg1/efg1 mutant cells exhibited opaque form, but shifted to white form in pH 4.5 media. The pH-dependent morphological switching is not blocked by further deletion of WOR1 in the efg1/efg1 mutant. Correlated with the phenotype, the opaque-phase-specific gene OP4 was induced in efg1/efg1 mutant cells when cultured in pH 6.8 media, and was repressed in pH 4.5 media. Consistently, the MTLa efg1/efg1 mutant cells could mate efficiently with MTL alpha cells in pH 6.8 media, but poorly in pH 4.5 media. Ectopic expression of the Rim101-405 allele in the efg1/efg1 mutant helped to bypass the pH restriction on white-opaque switching and show opaque form in both neutral and acidic media. We proposed that relief of the Efg1 repression enables C. albicans to undergo white-opaque switching in pH-dependent regulation mediated by Rim101-signaling pathway.