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EHEC 0157 Pathogenesis;Ovine and Animal Model Studies. - OZ0706

Description
Escherichia coli O157:H7 is recognised as the causal agent of a number of severe human diseases which are potentially fatal, particularly to the very young, the old and immuno-compromised. Studies indicate prevalence of Escherichia coli O157:H7 in healthy cattle with increasing evidence for persistence resulting in long-term sporadic excretion and seasonal infection of sheep. A model for the in vivo persistence in sheep has been established at VLA Weybridge. Evidence that known human virulence determinants of Escherichia coli O157:H7 play a minor role only in persistence is being derived from current studies, an understanding of these factors is needed to develop intervention strategies.

E. coli 0157:H7 are a group of emerging zoonotic pathogens of worldwide importance. In humans they cause acute gastroenteritis and haemorrhagic colitis a frequent complication of which is haemolytic uraemic syndrome which may leads to mortality. Meat products derived from cattle in which intestinal colonisation occurs in the absence of overt disease are considered to be a major source of infection.

Limitations to the control of the disease arise because of inadequate information on the virulence mechanisms of the causation bacteria. This project addressess this problem. The aim is to identify bacterial and host factors involved in colonisation of the bovine intestine by EHEC and particularly E. coli 0157:H7. Calves, bovine ligated intestinal loops and bovine intestinal organ cultures will be infected with wild-type and defined mutants of different EHEC strains and bacterial and host factors involved in colonisation, adhension, lesion formation and diarrhoea production will be identified.

This approach will provide insight into the molecular basis of the EHEC colonisation and disease processes and may identify bacterial proteins which could be incorporated into sub-unit or vector-based vaccines. It could also lead to the development of novel biological control methods not based on vaccination. The research is in support of MAFF policy on food safety. The strategic aim is to provide information which can be used to reduce EHEC in cattle and prevent their transmission to humans.
Objective
Obj. No. Completed by date Description

01
31:03:00
To undertake ovine pathogenesis studies with EHEC O157

Perhaps the most pressing objective is to gain an insight into the pathogenesis of EHEC O157 in the ovine as this animal host has been increasingly implicated as a major source but about which very little is known.


02
31:03:01
To develop an animal model and in vitro surrogate model to test the pathogenic potential of O157 strains

At present, there is no method to reliably test for the pathogenic potential of any O157 isolate. It is a pressing need to be able to relate current (and newly proposed) typing scheme information to the ability or otherwise of an isolate to cause a pathologic effect. This objective seeks to provide such a simple and reproducible system.


03
31:03:02
To develop a simple animal model to support studies into the molecular basis of persistence of O157 in farm animals

EHEC O157 does not cause any pathologic effect in the older bovine (and ovine presumably but as yet unproven) and yet persist in these hosts. Certain key pathogenic determinants of O157 (LEE, Eae, TIR, VTs, Hly etc) have been well characterised but, because attaching and effacing lesions are not in evidence in affected bovines, these factors may not come into play in the older animal. Indeed, it is suggested that O157 may persist as a commensal. Thus, it is essential to develop simple systems to screen mutants for their inability to persist in order to gain an understanding at the molecular level of this important factor. The objective is to develop a laboratory animal persistence model.

Project Documents
• Final Report : EHEC 0157 Pathogenesis: ovine and other animal model studies   (100k)
Time-Scale and Cost
From: 1999

To: 2004

Cost: £374,377
Contractor / Funded Organisations
Veterinary Laboratories Agency
Keywords
Animal Health              
Biotechnology              
E.coli O157              
GM Non-Food              
Plants and Animals              
Transmission              
Zoonoses              
Fields of Study
Animal Health