Roles of the Transcription Factors Sfl2 and Efg1 in White-Opaque Switching in a/α Strains of Candida albicans

Candida albicans remains the most pervasive fungal pathogen colonizing humans. The majority of isolates from hosts are heterozygous at the mating type locus (MTLa/alpha), and a third of these have recently been shown to be capable of switching to the opaque phenotype. Here we have investigated the roles of two transcription factors (TFs) Sfl2 and Efg1, in repressing switching in a/alpha strains. Deleting either gene results in the capacity of a/alpha cells to switch to opaque en masse under facilitating environmental conditions, which include N-acetylglucosamine (GlcNAc) as the carbon source, physiological temperature (37 degrees C), and high CO2 (5%). These conditions are similar to those in the host. Our results further reveal that while glucose is a repressor of sfl2 Delta and efg1 Delta switching, GlcNAc is an inducer. Finally, we show that when GlcNAc is the carbon source, and the temperature is low (25 degrees C), the efg1 Delta mutants, but not the sfl2 Delta mutants, form a tiny, elongate cell, which differentiates into an opaque cell when transferred to conditions optimal for a/alpha switching. These results demonstrate that at least two TFs, Sfl2 and Efg1, repress switching in a/alpha cells and that a/alpha strains with either an sfl2 Delta or efg1 Delta mutation can switch en masse but only under physiological conditions. The role of opaque a/alpha cells in commensalism and pathogenesis must, therefore, be investigated. IMPORTANCE More than 95% of Candida albicans strains isolated from humans are MTLa/alpha, and approximately a third of these can undergo the white-to-opaque transition. Therefore, besides being a requirement for MTL-homozygous strains to mate, the opaque phenotype very likely plays a role in the commensalism and pathogenesis of nonmating, a/alpha populations colonizing humans.