title: The transcription factor Flo8 mediates CO2 sensing in the human fungal pathogen Candida albicans.
abstract: Physiological levels of CO(2) have a profound impact on prominent biological attributes of the major fungal pathogen of humans, Candida albicans. Elevated CO(2) induces filamentous growth and promotes white-to-opaque switching. However, the underlying molecular mechanisms of CO(2) sensing in C. albicans are insufficiently understood. Here we identify the transcription factor Flo8 as a key regulator of CO(2)-induced morphogenesis in C. albicans by screening a gene null mutant library. We show that Flo8 is required for CO(2)-induced white-to-opaque switching, as well as for filamentous growth. Ectopic expression of FLO8 hypersensitizes C. albicans cells to the elevated CO(2) levels. Furthermore, we demonstrate that CO(2) signaling 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 CO(2) sensing 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 CO(2) sensing in pathogenic fungi that have important implications for higher organisms.
authors.affiliation: State Key Laboratory of Mycology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Han
authors.initials: H
authors.lastname: Du
authors.forename: Guobo
authors.initials: G
authors.lastname: Guan
authors.forename: Jing
authors.initials: J
authors.lastname: Xie
authors.forename: Fabien
authors.initials: F
authors.lastname: Cottier
authors.forename: Yuan
authors.initials: Y
authors.lastname: Sun
authors.forename: Wei
authors.initials: W
authors.lastname: Jia
authors.forename: Fritz A
authors.initials: FA
authors.lastname: Mühlschlegel
authors.forename: Guanghua
authors.initials: G
authors.lastname: Huang
mesh_terms: D000262:Adenylyl Cyclases / Q000235:genetics / Q000378:metabolism; D002176:Candida albicans / Q000254:growth & development / Q000378:metabolism / Q000502:physiology*; D002245:Carbon Dioxide / Q000502:physiology*; D000242:Cyclic AMP / Q000378:metabolism*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism; D015966:Gene Expression Regulation, Fungal; D009024:Morphogenesis; D009687:Nuclear Proteins; D015398:Signal Transduction; D015534:Trans-Activators; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D004268:DNA-Binding Proteins; C121438:EFG1 protein, Candida albicans; D005656:Fungal Proteins; D009687:Nuclear Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D002245:Carbon Dioxide; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D000262:Adenylyl Cyclases