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When colonising host-niches or non-animated medical devices, individual cells of the fungal pathogen  Candida albicans  expand into significant biomasses. Here we show that within such biomasses, fungal metabolically generated CO 2  acts as a communication molecule promoting the switch from yeast to filamentous growth essential for  C. albicans  pathology. We find that CO 2 -mediated intra-colony signalling involves the adenylyl cyclase protein (Cyr1p), a multi-sensor recently found to coordinate fungal responses to serum and bacterial peptidoglycan. We further identify Lys 1373 as essential for CO 2 /bicarbonate regulation of Cyr1p. Disruption of the CO 2 /bicarbonate receptor-site interferes selectively with  C. albicans  filamentation within fungal biomasses. Comparisons between the  Drosophila melanogaster  infection model and the mouse model of disseminated candidiasis, suggest that metabolic CO 2  sensing may be important for initial colonisation and epithelial invasion. Our results reveal the existence of a gaseous  Candida  signalling pathway and its molecular mechanism and provide insights into an evolutionary conserved CO 2 -signalling system.

CO2 Acts as a Signalling Molecule in Populations of the Fungal Pathogen Candida albicans