“
“Background Salmonella diversified from a common ancestor with E. coli approx. 100 million years ago [1]. This diversification was associated with the acquisition of genes which increased the virulence of Salmonella and enabled it to interact with its hosts and SB525334 colonise the intestinal tract of animals in a different way than E. coli did. The genomic sequences of E. coli and S. enterica serovars Typhi and Typhimurium have been known since 1997 and 2001, respectively [2–4] and genes which are absent in E. coli and are necessary for the full virulence expression of Salmonella are therefore relatively well described. Most of them are

clustered at specific parts of the Salmonella chromosome called pathogeniCity islands. There are 5 major pathogeniCity islands in the Salmonella enterica chromosome but only 4 of them, with SPI-2 absent, in the chromosome of Salmonella bongori, a second species

belonging to the genus Salmonella [5]. The major pathogeniCity islands include SPI-1, SPI-2, SPI-3, SPI-4 and SPI-5. The SPI-1 and SPI-2 genes code for proteins forming the type III secretion system (T3SS) which enable the transport of S. enterica proteins from the bacterial cell directly into the cytosol of eukaryotic cells. The SPI-1 encoded T3SS Cyclosporin A concentration is required for the transport of S. enterica proteins across the cytoplasmic membrane of a host cell into its cytosol where they induce cytoskeletal rearrangements resulting in the uptake of S. enterica even by non-phagocytic cells [6]. In addition, it has been reported that SPI-1 genes, independent of cell invasion, induce macrophage cytotoxiCity [7]. Interestingly, neither of these functions is required for the S. Typhimurium

virulence for Balb/C mice since a mutant without the whole SPI-1 was as virulent as the control wild type strain [8]. SPI-2 encoded T3SS is required for the transport of S. enterica proteins across the phagosomal membrane and increases S. enterica survival inside phagocytic cells [9, 10]. The function of genes localised on the remaining SPIs is less well CP-868596 characterised; SPI-3 genes are involved both in gut colonisation due to MisL-dependent fibronectin binding and intracellular survival due to high-affinity magnesium transport encoded by mgtABC [11, 12]. SPI-4 genes are required for the Megestrol Acetate intestinal phase of disease by coding for non-fimbrial adhesin [13], and the genes localised in SPI-5 are co-regulated with either SPI-1 or SPI-2 genes and therefore code for effector proteins transported by either of these T3SS [14]. However, the vast majority of this information has been obtained in a mouse model and S. Typhimurium and much less data are available for S. Enteritidis and pigs, cattle or poultry although these animal species, and poultry in particular, represent major reservoirs of Salmonella for the human population in Europe. The roles of different SPI genes in the virulence S. enterica for chickens are less well understood.