MACROPHAGE-DEPENDENT INDUCTION OF THE SALMONELLA PATHOGENICITY ISLAND2 TYPE-III SECRETION SYSTEM AND ITS ROLE IN INTRACELLULAR SURVIVAL

Salmonella pathogenicity island 2 (SPI-2) encodes a putative type III secretion system necessary for systemic infection in animals. We have investigated the transcriptional organization and regulation of SPI-2 by creating gfp fusions throughout the entire gene cluster. These gfp fusions demonstrated that SPI-2 genes encoding structural, regulatory and previously uncharacterized putative secreted proteins are preferen tially expressed in the intracellular environment of the host macropha ge. Furthermore, the transcription of these genes within host cells wa s dependent on the two-component regulatory system SsrA/SsrB and an ac idic phagosomal environment. Most SPI-2 mutants failed to replicate to the same level as wild-type strains in murine macrophages and human e pithelial cells. In orally infected mice, SPI-2 mutants colonized the Peyer's patches but did not progress to the mesenteric lymph nodes. We conclude that SPI-2 genes are specifically expressed upon entry into mammalian cells and are required for intracellular growth in host cell s in vivo and in vitro.