Award details

Association of VTEC O157 and O26 strains with the bovine intestinal mucosa ex vivo.

Reference	BB/E025277/1
Principal Investigator / Supervisor	Dr Francis Dziva
Co-Investigators / Co-Supervisors
Institution	The Pirbright Institute
Department	Avian Infectious Diseases
Funding type	Research
Value (£)	56,167
Status	Completed
Type	Research Grant
Start date	01/04/2008
End date	31/03/2012
Duration	48 months

Abstract

O157 and non-O157 VTEC are important zoonotic pathogens. Cattle contaminated with VTEC are the major reservoir for human infection. However, little is currently known about the mechanisms involved colonisation of the bovine gut. Progress has been slow because adherent VTEC bacteria are seen only infrequently following experimental challenges. The ability of VTEC to cause disease is associated with the capacity to cause attaching and effacing (A/E) lesions and to elaborate Shiga toxin. Little is currently known about A/E lesion formation during colonisation of the bovine gut. The genes required for A/E lesion formation by VTEC O157:H7 in vitro are carried on the LEE, which encodes the effector Tir and the adhesin intimin, and prophage CP-933U, which encodes TccP. Binding of intimin to the extracellular domain of Tir and of TccP to the C-terminus of Tir activates N-WASP and trigger A/E lesion. In vivo evidence show that intimin and Tir are essential for colonisation of the bovine gut while TccP have an accessory function. In VTEC O26, phosphorylation of Tir leads to recruitment of Nck and activation of N-WASP. However, as VTEC O26 express TccP2 it can induce A/E lesions by alternative pathways. Intestinal in vitro organ cultures (IVOC) provide a powerful model to study bacterial interaction with mucosal surfaces. We recently developed a robust bovine IVOC (bIVOC) of terminal ileum, terminal colon and terminal rectum, infection of which resulted in colonisation and A/E lesion formation. In this project we aim to exploit the bIVOC to study the bovine phase of VTEC infection cycle. We will investigate: the association of prototype VTEC O157 and O26 strains; the affects of animal age; colonisation characteristics of field O157 and O26 VTEC isolates; how passage through the GI affects colonisation dynamics; the composition of the actin-rich pedestal in bIVOC infected with VTEC O26 and O157 and the role Tir and TccP/TccP2 in colonisation and A/E lesion formation.

Summary

Please see case uploaded by Prof. Frankel (F442400).

Committee	Closed Committee - Agri-food (AF)
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

Associated awards:

BB/E025153/1 Association of VTEC O157 and O26 strains with the bovine intestinal mucosa ex vivo

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