Hall, RA;
De Sordi, L;
Maccallum, DM;
Topal, H;
Eaton, R;
Bloor, JW;
Robinson, GK;
... Mühlschlegel, FA; + view all
(2010)
CO(2) acts as a signalling molecule in populations of the fungal pathogen Candida albicans.
PLoS Pathog
, 6
(11)
, Article e1001193. 10.1371/journal.ppat.1001193.
![[thumbnail of 1340844.pdf]](https://discovery.ucl.ac.uk/style/images/fileicons/application_pdf.png) Preview |
PDF
1340844.pdf Download (2MB) |
Abstract
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.
| Type: | Article |
|---|---|
| Title: | CO(2) acts as a signalling molecule in populations of the fungal pathogen Candida albicans. |
| Location: | United States |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1371/journal.ppat.1001193 |
| Publisher version: | http://dx.doi.org/10.1371/journal.ppat.1001193 |
| Language: | English |
| Additional information: | © 2010 Hall et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Funding: This work was funded by the MRC, BBSRC and Nuffield Foundation (all to FAM). Work in the CS laboratory was funded by DFG priority program 1160 (grant STE1701/2 to CS). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. |
| Keywords: | Adenylate Cyclase, Animals, Bicarbonates, Biomass, Blotting, Southern, Blotting, Western, Candida albicans, Candidiasis, Carbon Dioxide, Cell Communication, Disease Models, Animal, Drosophila melanogaster, Female, Mice, Mice, Inbred BALB C, Mutagenesis, Site-Directed, Peptidoglycan, RNA, Messenger, Reverse Transcriptase Polymerase Chain Reaction, Saccharomyces cerevisiae, Signal Transduction, Survival Rate |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences |
| URI: | https://discovery.ucl.ac.uk/id/eprint/1340844 |
Archive Staff Only
 |
View Item |
