Variation in transcription regulator expression underlies differences in white–opaque switching between the SC5314 reference strain and the majority of Candida albicans clinical isolates

Abstract

Abstract Candida albicans, a normal member of the human microbiome and an opportunistic fungal pathogen, undergoes several morphological transitions. One of these transitions is white–opaque switching, where C. albicans alternates between 2 stable cell types with distinct cellular and colony morphologies, metabolic preferences, mating abilities, and interactions with the innate immune system. White-to-opaque switching is regulated by mating type; it is repressed by the a1/α2 heterodimer in a/α cells, but this repression is lifted in a/a and α/α mating type cells (each of which are missing half of the repressor). The widely used C. albicans reference strain, SC5314, is unusual in that white–opaque switching is completely blocked when the cells are a/α; in contrast, most other C. albicans a/α strains can undergo white–opaque switching at an observable level. In this paper, we uncover the reason for this difference. We show that, in addition to repression by the a1/α2 heterodimer, SC5314 contains a second block to white–opaque switching: 4 transcription regulators of filamentous growth are upregulated in this strain and collectively suppress white–opaque switching. This second block is missing in the majority of clinical strains, and, although they still contain the a1/α2 heterodimer repressor, they exhibit a/α white–opaque switching at an observable level. When both blocks are absent, white–opaque switching occurs at very high levels. This work shows that white–opaque switching remains intact across a broad group of clinical strains, but the precise way it is regulated and therefore the frequency at which it occurs varies from strain to strain.