The transcription factor Flo8 mediates CO2sensing in the human fungal pathogenCandida albicans

Abstract

Physiological levels of CO2have a profound impact on prominent biological attributes of the major fungal pathogen of humans, Candida albicans. Elevated CO2induces filamentous growth and promotes white-to-opaque switching. However, the underlying molecular mechanisms of CO2sensing in C. albicans are insufficiently understood. Here we identify the transcription factor Flo8 as a key regulator of CO2-induced morphogenesis in C. albicans by screening a gene null mutant library. We show that Flo8 is required for CO2-induced white-to-opaque switching, as well as for filamentous growth. Ectopic expression of FLO8 hypersensitizes C. albicans cells to the elevated CO2levels. Furthermore, we demonstrate that CO2signaling in C. albicans involves two pathways: the already reported cAMP/protein kinase A and another major one that is unidentified. The two pathways converge on the transcription factor Flo8, which is the master regulator of CO2sensing in C. albicans and plays a critical role in regulation of white-to-opaque switching and filamentous growth. Our findings provide new insights into the understanding of CO2sensing in pathogenic fungi that have important implications for higher organisms.