CO(2) acts as a signalling molecule in populations of the fungal pathogen Candida albicans.
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.
School of Biosciences, University of Kent, Canterbury, Kent, UK.
Rebecca A
RA
Hall
Luisa
L
De Sordi
Donna M
DM
Maccallum
Hüsnü
H
Topal
Rebecca
R
Eaton
James W
JW
Bloor
Gary K
GK
Robinson
Lonny R
LR
Levin
Jochen
J
Buck
Yue
Y
Wang
Neil A R
NA
Gow
Clemens
C
Steegborn
Fritz A
FA
Mühlschlegel
D000262:Adenylyl Cyclases / Q000378:metabolism*; D000818:Animals; D001639:Bicarbonates / Q000378:metabolism; D018533:Biomass; D015139:Blotting, Southern; D015153:Blotting, Western; D002176:Candida albicans / Q000472:pathogenicity*; D002177:Candidiasis / Q000378:metabolism* / Q000382:microbiology; D002245:Carbon Dioxide / Q000378:metabolism*; D002450:Cell Communication / Q000502:physiology*; D004195:Disease Models, Animal; D004331:Drosophila melanogaster / Q000502:physiology; D005260:Female; D051379:Mice; D008807:Mice, Inbred BALB C; D016297:Mutagenesis, Site-Directed; D010457:Peptidoglycan / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012441:Saccharomyces cerevisiae / Q000472:pathogenicity*; D015398:Signal Transduction; D015996:Survival Rate
D001639:Bicarbonates; D010457:Peptidoglycan; D012333:RNA, Messenger; D002245:Carbon Dioxide; D000262:Adenylyl Cyclases