MTL-independent phenotypic switching in Candida tropicalis and a dual role for Wor1 in regulating switching and filamentation.

Phenotypic switching allows for rapid transitions between alternative cell states and is important in pathogenic fungi for colonization and infection of different host niches. In Candida albicans, the white-opaque phenotypic switch plays a central role in regulating the program of sexual mating as well as interactions with the mammalian host. White-opaque switching is controlled by genes encoded at the MTL (mating-type-like) locus that ensures that only a or α cells can switch from the white state to the mating-competent opaque state, while a/α cells are refractory to switching. Here, we show that the related pathogen C. tropicalis undergoes white-opaque switching in all three cell types (a, α, and a/α), and thus switching is independent of MTL control. We also demonstrate that C. tropicalis white cells are themselves mating-competent, albeit at a lower efficiency than opaque cells. Transcriptional profiling of C. tropicalis white and opaque cells reveals significant overlap between switch-regulated genes in MTL homozygous and MTL heterozygous cells, although twice as many genes are white-opaque regulated in a/α cells as in a cells. In C. albicans, the transcription factor Wor1 is the master regulator of the white-opaque switch, and we show that Wor1 also regulates switching in C. tropicalis; deletion of WOR1 locks a, α, and a/α cells in the white state, while WOR1 overexpression induces these cells to adopt the opaque state. Furthermore, we show that WOR1 overexpression promotes both filamentous growth and biofilm formation in C. tropicalis, independent of the white-opaque switch. These results demonstrate an expanded role for C. tropicalis Wor1, including the regulation of processes necessary for infection of the mammalian host. We discuss these findings in light of the ancestral role of Wor1 as a transcriptional regulator of the transition between yeast form and filamentous growth.