CO2 acts as a signalling molecule in Candida albicans

Candida albicans Candida albicans is the predominant fungal pathogen of humans. In healthy individuals C. albicans is a commensal inhabitant of the gastrointestinal, oral and vaginal tracts. C. albicans can cause superficial infections which, although not life threatening, provide discomfort to the individual and require treatment with antifungals which is a constant drain on hospitals resources. However, C. albicans infections are life threatening when the individual’s immune system becomes compromised as a result of age, cancer, chemotherapy hospitalisation and AIDS. Under these circumstances superficial infections may readily develop into systemic disease where mortality rates are reported to be up to 40%, which is higher than those for most bacterial infections.

Pathogenic microorganisms can produce a variety of secondary metabolites and signalling molecules which can affect the host, or provide them with a selective advantage against competing commensal organisms. This paper demonstrates that gaseous, metabolically generated CO2 can serve as a signalling molecule to enhance the organism’s virulence during infection establishment by using the fungal pathogen Candida albicans as a model. The researchers identified a CO2 receptor site within the catalytic domain of the soluble adenylyl cyclase, Cyr1p, which is critical for CO2 sensing and hence virulence of the organism. CO2 sensing is conserved in a variety of pathogenic species, and increased levels have been shown to suppress the host’s immune system. CO2 sensing may represent a mechanism to enhance C. albicans virulence when the host’s immune system is suppressed.

CO2 Acts as a Signalling Molecule in Populations of the Fungal Pathogen Candida albicans. (2010) PLoS Pathog 6(11): e1001193. doi:10.1371/journal.ppat.1001193
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 CO2 acts as a communication molecule promoting the switch from yeast to filamentous growth essential for C. albicans pathology. We find that CO2-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 CO2/bicarbonate regulation of Cyr1p. Disruption of the CO2/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 CO2 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 CO2-signalling system.

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