GENES ENCODING PUTATIVE EFFECTOR PROTEINS OF THE TYPE-III SECRETION SYSTEM OF SALMONELLA PATHOGENICITY ISLAND 2 ARE REQUIRED FOR BACTERIAL VIRULENCE AND PROLIFERATION IN MACROPHAGES

The type III secretion system of Salmonella pathogenicity island 2 (SP I-2) is required for systemic infection of this pathogen in mice, Clon ing and sequencing of a central region of SPI-2 revealed the presence of genes encoding putative chaperones and effector proteins of the sec retion system. The predicted products of the sseB, sseC and sseD genes display weak but significant similarity to amino acid sequences of Es pA, EspD and EspB, which are secreted by the type III secretion system encoded by the locus of enterocyte effacement of enteropathogenic Esc herichia coil. The transcriptional activity of an sseA::luc fusion gen e was shown to be dependent on ssrA, which is required for the express ion of genes encoding components of the secretion system apparatus. St rains carrying nonpolar mutations in sseA, sseB or sseC were severely attenuated in virulence, strains carrying mutations in sseF or sseG we re weakly attenuated, and a strain with a mutation in sseE had no dete ctable virulence defect. These phenotypes were reflected in the abilit y of mutant strains to grow within a variety of macrophage cell types: strains carrying mutations in sseA, sseB or sseC failed to accumulate , whereas the growth rates of strains carrying mutations in sseE, sseF or sseG were only modestly reduced. These data suggest that, in vivo, one of the functions of the SPI-2 secretion system is to enable intra cellular bacterial proliferation.