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Cyclic-diGMP signalling and environmental adaptation in Pseudomonas aeruginosa

Reference	BB/C509082/1
Principal Investigator / Supervisor	Professor Paul Williams
Co-Investigators / Co-Supervisors	Professor David Barrett, Professor Miguel Camara, Dr Stephan Heeb
Institution	University of Nottingham
Department	Inst of Infections and Immunity
Funding type	Research
Value (£)	276,156
Status	Completed
Type	Research Grant
Start date	01/10/2004
End date	31/12/2007
Duration	39 months

Abstract

Pseudomonas aeruginosa is an ubiquitous Gram-negative bacterium which possesses a 6.3MB genome. Some 10 per cent of the genome is devoted to regulatory genes and although the majority of these are of unknown function, they point to the existence of a highly sophisticated gene regulatory network which facilitates the extra-ordinary adaptability of P. aeruginosa to diverse environments. Previously we have shown that the small RNA-binding protein RsmA is a negative control element in the production of e.g exoproteases, pyocyanin, hydrogen cyanide, PA-IL lectin and quorum sensing signal molecules. P. aeruginosa rsmA mutants are unable to swarm, and we discovered a gene, PA2567 which restores swarming motility. Sequence analysis of the PA2567 gene product indicates that it contains three predicted domains GGDEF, EAL and GAF associated with an intra-cellular signalling pathway involving cyclic-di-guanylate (c-di-GMP). The P. aeruginosa genome contains some 33 predicted proteins with a GGDEF domain and 21 containing an EAL domain most of which are of unknown function but are predicted to be involved in c-di-GMP signalling. Recently two P. aeruginosa GGDEF and EAL containing proteins, WspR and FimX have been identified from mutant screens as playing roles in twitching motility (FimX) and the regulation of colony morphology, swarming, swimming and biofilm formation (WspR) respectively. P. aeruginosa therefore appears to possess an extensive intra-cellular signalling network employing c-di-GMP as the cognate signal molecule which is likely to make an important contribution to its adaptation and survival. We propose to use PA2567 as a useful starting point to begin exploration of the contribution of the c-di-GMP regulatory network to the biology of Pseudomonas and the biochemical functions of P. aeruginosa proteins with predicted guanylate cyclase and phosphodiesterase domains. We propose to build on our preliminary work by (a) defining the roles of PA2567 and the GGDEF/EAL-containing proteins to the phenotype of P. aeruginosa, (b) by employing functional genomic (transcriptomic proteomic and metabolomic) approaches to gain novel insights into the extent of the c-di-GMP signalling network, (c) by determining the biochemical functions of PA2567 which contains putative diguanylate cyclase (GGDEF) and phosphodiesterase (EAL) domains, (d) by investigating the mechanism by which PA2567 is regulated and (e) to establish the regulatory links between the RsmA and c-di-GMP signalling pathways.

Summary

unavailable

Committee	Closed Committee - Plant & Microbial Sciences (PMS)
Research Topics	X – not assigned to a current Research Topic
Research Priority	X – Research Priority information not available
Research Initiative	X - not in an Initiative
Funding Scheme	X – not Funded via a specific Funding Scheme

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