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

PLoS Pathogens

Jochen Buck¹  Yue Wang¹  Fritz A. Mühlschlegel²  Rebecca Eaton²  Neil A. R. Gow³  Gary K. Robinson⁴  Lonny R. Levin⁴  Donna M. MacCallum⁴  James W. Bloor⁴  Rebecca A. Hall⁴  Hüsnü Topal⁵  Luisa De Sordi⁵  Clemens Steegborn⁵ 

[1] Department of Pharmacology, Weill Medical College of Cornell University, New York, New York, United States of America;Department of Physiological Chemistry, Ruhr-University Bochum, Bochum, Germany;Institute of Molecular and Cell Biology, Agency for Science, Technology and Research, Proteos, Singapore;School of Biosciences, University of Kent, Canterbury, Kent, United Kingdom;School of Medical Sciences, Institute of Medical Sciences, University of Aberdeen, Aberdeen, United Kingdom

关键词: Carbon dioxide;    C;    ida albicans;    Bicarbonates;    Fungal pathogens;    Adenylyl cyclase;    Adenylyl cyclase signaling cascade;    Drosophila melanogaster;    Pathogenesis;   

DOI  :  10.1371/journal.ppat.1001193

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

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.

【 授权许可】

CC BY