Salmonella Pathogenesis in Cattle and Pigs

Salmonellosis is now one of the most important bacterial diseases of man and animals in the U.K. and has important implications for human and animal health and welfare. The aim of this study is to characterise further the virulence factors influencing Salmonella pathogenesis and the host response to infection in cattle and pigs.<P>
The unique facilities of IAH, Compton will be exploited to study natural host/pathogen interactions at the molecular level. Cattle will be infected orally with wild type and mutant strains of S.typhimiurium and the faecal shedding of such strains quantified. Factors influencing intestinal colonisation will be identified and assessed for incorporation into a vaccine. Bovine and porcine ligated ileal loops will be infected with wild-type and defined mutant strains of different Salmonella serotypes The effect of infection on the host will be determined with respect to Salmonella-induced enteropathogenic and inflammatory responses. The role of specific genes in influencing such responses will be characterised. This approach will provide insight into the molecular basis of Salmonella pathogenesis, information which is essential for the design of effective and sustainable control measures and reduced reliance on the use of antibiotics. <P>

The research meets DEFRA policy requirements on food safety and animal health and welfare. The strategic aims are to safeguard food safety, reduce the impact of bacterial disease, develop effective vaccines that cross protect against all Salmonella serotypes and reduce the dependance on antibiotics which may lead to the emergence of more antibiotic resistant strains.
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Objectives:
<OL> <LI> Identify genes involved in Salmonella intestinal colonization.
<LI>Characterize Salmonella virulence factors involved in the induction of enteropathogenesis.
<LI>Elucidate the molecular basis of Salmonella serotype host specificity.Virulence gene expression, net growth and host cell targetting will be assessed for S. typhimurium, S. dublin, S gallinarum and S. choleraesuis in cattle and pigs.
<LI> Optimise the attenuation of live Salmonella vaccine strains. Combinations of attenuating mutations identified in 1-3 above will be assessed for the construction of vaccine strains.