Award details

Small molecule signalling in Campylobacter jejuni

Reference	BBS/E/F/00042194
Principal Investigator / Supervisor	Dr Neil Shearer
Co-Investigators / Co-Supervisors
Institution	Quadram Institute Bioscience
Department	Quadram Institute Bioscience Department
Funding type	Research
Value (£)	76,900
Status	Completed
Type	Institute Project
Start date	01/10/2008
End date	31/12/2009
Duration	15 months

Abstract

CbrR is an orphan response regulator found in all genome-sequenced species of Campylobacter, the leading bacterial cause of human gastroenteritis. CbrR contains 2 N-terminal phosphor-receiver domains predicted to play a regulatory function, and a C-terminal GGDEF domain. GGDEF domains are known to possess diguanylate cyclase (DGC) activity, synthesising the bacterial secondary messenger cyclic-dimeric-GMP (c-di-GMP), which has been implicated in regulating various phenotypes including; multicellular behaviour, cell differentiation and virulence. Campylobacter CbrR proteins can be divided into two subtypes, depending on whether the sequence derives from chicken colonisers or non-colonisers. In the non-colonisers (e.g. C. fetus) the protein contains a C-terminal GGDEF domain in which a highly conserved active-site motif is conserved. However in CbrR from chicken colonising species of Campylobacter this GGDEF motif is not completely conserved, although all other essential residues of the domain are. This sub-grouping of CbrRs, taken along with the fact that a cbrR mutant of C. jejuni (a chicken coloniser) shows increased sensitivity to bile and reduced ability to colonise chickens, suggests that CbrR is a key determinant of a Campylobacter species ability to colonise chickens. A full mechanistic understanding of the CbrR signalling pathway is therefore essential as it raises a real possibility for interventions to reduce the Campylobacter burden within the food chain. This aim of this project is to unravel the CbrR dependent signalling pathway and to determine mechanistically how this pathway leads to increased bile resistance. The enzymatic function of the CbrR GGDEF domain will be studied using in vitro and in vivo DGC assays and possible differences between proteins from C. jejuni and C. fetus will be explored. The role played by the receiver domains in regulating CbrR function will be examined using in vivo studies with site directed CbrR mutants in C. jejuni.

Summary

unavailable

Committee	Closed Committee - Plant & Microbial Sciences (PMS)
Research Topics	Animal Health, Microbial Food Safety, Microbiology
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

I accept the terms and conditions of use (opens in new window)

export PDF file

back to list new search