Adhesive properties which are essential for the invasion of animal cells and for the virulence of orally administered S. typhimurium are encoded on virulence plasmida of about 60 Mdal plasmid.
Our aim i s to isolate and characterize the adhesive substance and clone the adhesin gene for further study. Isolation will entail initial identification of unique envelopr proteins of plasmid bearing strains by two-dimensional gel electophoresis. The adhesin will be isolated by biochemical procedures coupled with the production and use of monoclonal antibody in affinity chromatography. The adhesin gene will be cloned into suitable cloning vectors and transformed into a S. typhimurium background for further study. This will include definitive studies on the role of adhesion employing insertionally inactivated nonadhesive mutants, and the distribution of the salmonella adhesin using cloned adhesin genes and specific adhesin antibody as probes. Cloning of the adhesive factor will enable us to define precisely its function in interaction with animal cell (including macrophage) receptors and the consequential induction of the animal cell's endocytic mechanisms. Of considerable interest is that in the mouse, resistance to salmonellae, Mycobacteria and Leishmania is specified by a single locus possibly involving macrophage activity. The identification of functions in resistance to salmonella will further studies on other intrcellular pathogens in terms of how salmonellae enter and circumvent killing by macrophages, and also provide needed insights of macrophage antibacterial function.
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