Identification of a novel Salmonella invasion locus homologous to Shigella ipgDE.

Genes essential for Salmonella typhimurium invasion have been localized to Salmonella pathogenicity island 1 (SPI1) on the chromosome. However, it is clear that other genes are required for the invasion process. Mutations that abolish the SPI1 invasion type III secretion system do not significantly reduce invasion into Chinese hamster ovary tissue culture cells. Two invasion defective mutants were isolated by screening 2,500 Tn10dTc insertion mutants of S. typhimurium in the tissue culture invasion assay. One of the invasion mutants, SVM167, has an insertion between centisomes 24.5 and 25.5 in an operon homologous to the ipgDEF operon of the Shigella flexneri and Shigella sonnei virulence plasmid. A second mutant, SVM168, has an insertion in an IS3-type element with homology to the Salmonella enteritidis IS1351 element and Yersinia enterocolitica IS1400 element from a high-pathogenicity island. Further characterization of SVM167 showed that culture supernatants from this mutant lack a previously uncharacterized protein that is also missing from culture supernatants of a SPI1 mutant, suggesting it can be secreted by the SPI1 type III secretion system. In addition, transcription of this operon, sigDE (Salmonella invasion gene), is dependent on the presence of sirA, an activator of hilA expression. HilA activates transcription of several of the SPI1 genes but does not appear to have a major role in activation of transcription from the sigDE promoter.