Entry into
intestinal epithelial cells is an essential feature in the
pathogenicity of
Salmonella typhi, which causes
typhoid fever in humans. This process requires intact motility and
secretion of the invasion-promoting Sip proteins, which are targets of the
type III secretion machinery encoded by the inv, spa and prg loci. During our investigations into the entry of S. typhi into cultured
epithelial cells, we observed that the
secretion of Sip proteins and
flagellin was
impaired in Vi-expressing strains. We report here that the production of Sip proteins,
flagellin and Vi
antigen is differentially modulated by the RcsB-RcsC regulatory system and
osmolarity. This regulation occurs at both
transcriptional and post-translational levels. Under low-osmolarity conditions, the transcription of iagA, invF and sipB genes is negatively controlled by the RcsB regulator, which probably acts in association with the viaB locus-encoded TviA protein. The cell surface-associated Vi
polysaccharide, which was maximally produced under these growth conditions, prevented the
secretion of Sip proteins and
flagellin. As the
NaCl concentration in the
growth medium was increased, transcription of iagA, invF and sipB was found to be markedly increased, whereas transcription of genes involved in Vi
antigen biosynthesis was greatly reduced. The expression of iagA, whose product is involved in invF and sipB transcription, occurred selectively during the exponential growth phase and was maximal in the presence of 300mM
NaCl. At this
osmolarity, large amounts of Sips and
flagellin were
secreted in culture supernatants. As expected from these results, and given the essential role of Sip proteins and motility in entry, RcsB and
osmolarity modulated the invasive capacity of S. typhi. Together, these findings might reflect the
adaptive response of S. typhi to the environments encountered during the different stages of
pathogenesis.
