Environmental and genetic regulation of white‐opaque switching in Candida tropicalis

Summary Phenotypic switching is a strategy by which microbial organisms adapt to environmental changes. The human fungal pathogens, Candida albicans and Candida tropicalis , are closely related species and capable of undergoing morphological transitions. C. albicans primarily exists in human or warm‐blooded animals as a commensal, whereas C. tropicalis not only exists as a commensal but also is widely distributed in the environment. In this study, we describe the environmental and genetic regulatory mechanisms of white‐opaque switching in C. tropicalis , which is associated with virulence and sexual mating. A comparative study with C. albicans demonstrated that C. tropicalis responds to environmental stimuli, such as elevated CO 2 levels and pH changes, in opposite manners. An acidic pH and elevated CO 2 levels promote the opaque phenotype in C. albicans but have an opposite effect in C. tropicalis , whereas alkaline pH conditions facilitate white‐to‐opaque switching and sexual mating in C. tropicalis . The conserved Rim101‐mediated pH sensing and Ras1‐cAMP/PKA signaling pathways are involved in this regulation. By screening an overexpression library of transcription factors, we identified 26 white‐opaque regulators, including WOR1 , AHR1 , EFG1 , CUP9 , BCR1 and SFL2 . Transcriptional analysis indicated that the pH sensing and Ras1‐cAMP/PKA signaling pathways and transcriptional regulators coordinately regulate white‐to‐opaque switching.