Molecular Basis of Salmonella Virulence

The Group has recently identified and characterised and currently is working on TTSS-1 secreted effector proteins (termed Sops for Salmonella outer proteins or Pips for Pathogenicity-island-encoded proteins) which are key virulence factors required for Salmonella invasion, induction of fluid secretion and inflammatory responses. <P>
Our objective is to understand how different Salmonella Sop and Pip effector proteins function inside host cells to elicit proinflammatory responses that lead to intestinal inflammation. We speculate that some Sops and Pips may be needed for the induction of signals leading to the attraction of PMN from the peripheral blood into the lamina propria, whereas, others may be involved in orchestrating the migration of PMNs across the epithelial monolayers. <P>
We will construct and use genetically defined Salmonella mutants in association with our biologically relevant model systems to examine the importance of effector proteins in enteropathogenicity. To enable further functional analyses, we will assemble eukaryotic expression plasmids encoding Sop and Pip effector proteins and assess effects mediated by their expression in cultured cells. We will localize effector proteins to specific cellular organelles and analyze the targeting signals and subsequent cellular responses. The rationale for this is based on the knowledge that different effector proteins (Yops) of Yersinia are targeted to different cellular compartments. <P>
Finally, we will assess the relevance of the data obtained in vitro by performing experimental Salmonella infections using the relevant animal model system and monitoring the responses elicited by such infections.