Sips, Sops, and SPIs but not STN influence Salmonella enteropathogenesis

The virulence factors influencing Salmonella-induced enteropathogenesis rem ain poorly characterised. The interactions of different serotypes of Salmon ella with bovine ileal mucosa have been characterised in the ligated ileal loop model. In a quantitative intestinal invasion assay Salmonella dublin, S. choleraesuis, S. gallinarum, and S. abortusovis strains were all recover ed from ileal mucosa, either with or without Peyer's patches in similar num bers. This observation suggests that the magnitude and route of intestinal invasion does not mediate Salmonella serotype host specificity. Despite bei ng equally invasive there was a clear hierarchy in the enteropathogenicity of these serotypes. The magnitude of the enteropathogenic responses did not correlate to serotype host specificity. These observations implicate undef ined serotype specific factors in influencing enteropathogenicity independe ntly of intestinal invasion. Disruption of genes in Salmonella Pathogenicit y Island (SPI) 1 of S. typhimurium and S. dublin blocked the secretion of S almonella Invasion Proteins (Sips) and Salmonella Outer Proteins (Sops). Th ese mutants were significantly less invasive and enteropathogenic then the wild type strain in ligated ileal loops. Disruption of sopB and sopD signif icantly reduced enteropathogenesis, but without influencing intestinal inva sion. These two genes appear to act in concert. Surprisingly, disruption of stn, the Salmonella enterotoxin gene cloned on the basis of its homology t o cholera toxin, did not influence enteropathogenesis. SopB was mapped to t he 20 centisome of S. typhimurium and is flanked by 5 genes that are organi sed in a manner typical of a pathogenicity island, which we have termed SPI -5. Mutation of the other genes in SPI-5 also attenuated enteropathogenesis but not virulence for mice, suggesting SPI-5 is a key locus specifically i nfluencing Salmonella enteropathogenesis.