VTEC, especially Escherichia coli O157:H7 may cause Haemolytic Uraemic Syndrome (HUS), Haemorrhagic Colitis (HC), Thrombotic Thrombocytopaenic Purpura and sporadic Infantile Diarrhoea in humans. These syndromes are potentially fatal in the young, elderly and immuno-compromised. Epidemiological studies show that ruminants, especially cattle and sheep, are significant sources for the transmission and maintenance of E. coli O157:H7. Recent data indicate that E. coli O157 colonises both cattle and sheep by Locus of Enterocyte Effacement (LEE) dependent and LEE-independent mechanisms, possibly showing a specific tropism to the lymphoid tissue of the rectum (RAJ) in cattle, but not sheep. It is established that E. coli O157 possess a number of key immune and host cell response modulators. However, the contribution of the host immune responses specially relating to clearance remains unclear and confounded by a very recent finding indicating that concurrent parasitic infection is associated with E. coli O157 induced AE lesion formation and very high faecal shedding. Thus, the picture of ruminant colonisation by E. coli O157 is complex. <P>
In order to devise interventions to reduce colonisation of ruminants by O157, it is essential that detailed knowledge of all factors that influence colonisation are understood. Thus the specific aims of this proposal are: <OL> <LI> To determine by signature tagged and directed mutagenesis the contribution of non-LEE encoded factors of EHEC O157:H7 in colonisation and persistence<LI> To evaluate the host responses in the various models used in a above <LI> To establish whether concurrent infection with parasites enhances colonisation and persistence of E. coli O157:H7 in sheep. </ol> Finally, written reports for DEFRA and peer reviewed publications with specific emphasis upon providing information that will inform a greater understanding of the risks to human health associated with E. coli O157 will prepared.