Showing papers by "Timothy S. Wallis published in 1999"

SIPS, SOPS, and SPIs but not STN Influence Salmonella Enteropathogenesis

Abstract: The virulence factors influencing Salmonella-induced enteropathogenesis remain poorly characterised. The interactions of different serotypes of Salmonella 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. abor-tusovis strains were all recovered from ileal mucosa, either with or without Peyer’s patches in similar numbers. This observation suggests that the magnitude and route of intestinal invasion does not mediate Salmonella serotype host specificity. Despite being 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 undefined serotype specific factors in influencing enteropathogenicity independently of intestinal invasion. Disruption of genes in .Salmonella Pathogenicity Island (SPI) 1 of S. typhimurium and S. dublin blocked the secretion of Salmonella Invasion Proteins (Sips) and Salmonella Outer Proteins (Sops). These mutants were significantly less invasive and enteropathogenic then the wild type strain in ligated ileal loops. Disruption of sopB and sopD significantly reduced enteropathogenesis, but without influencing intestinal invasion. These two genes appear to act in concert. Surprisingly, disruption of stn, the Salmonella enterotoxin gene cloned on the basis of its homology to cholera toxin, did not influence enteropathogenesis. SopB was mapped to the 20 centisome of S. typhimurium and is flanked by 5 genes that are organised 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 influencing Salmonella enteropathogenesis.

Attenuation of bacteria: materials and methods relating thereto

Abstract: Attenuated microorganisms are prepared by mutating one or more genes selected from sopA, sopD, sipA, or a gene from within the pathogenicity island SPI-5, when the microorganism is Salmonella, or one or more homologous genes which correspond to said Salmonella genes, when the microorganism is another enteric bacteria. In comparison with the wild-type strains, the attenuated microorganisms have a reduced enteropathogenicity but substantially the same invasiveness. The attenuated microorganisms can be administered as vaccines against infection by enteric bacteria. Polypeptides encoded by sopA, pipD, orfX, pipC, pipB and pipA genes, variants thereof, and nucleic acids encoding those polypeptides, are also provided.