Epithelial cell contact-induced alterations in Salmonella enterica serovarTyphi lipopolysaccharide are critical for bacterial internalization

The invasion of Pseudomonas aeruginosa and Salmonella enterica serovar Typh i into epithelial cells depends on the cystic fibrosis transmembrane conduc tance regulator (CFTR) protein as an epithelial receptor. In the case of P. aeruginosa, the bacteria ligand for CFTR is the outer core oligosaccharide portion of the lipopolysaccharide (LPS). To determine whether serovar Typh i LPS is also a bacterial ligand mediating internalization, we used both P. aeruginosa and serovar Typhi LPS as a competitive inhibitor of serovar Typ hi invasion into the epithelial cell line T84. P. aeruginosa LPS containing a complete core efficiently inhibited serovar Typhi invasion. However, nei ther killed wild-type Typhi cells nor purified LPS were effective inhibitor s. LPS from mutant Typhi strains defective in O side-chain synthesis, but w ith an apparently normal core, was capable of inhibiting invasion, but LPS obtained from a deeper rough mutant strain with alterations in fast-migrati ng core, oligosaccharide failed to inhibit invasion. Lastly, exposure of wi ld-type serovar Typhi to T84 cultures before heat killing resulted in a str uctural alteration in its LPS that allowed the heat-killed cells to inhibit invasion of wild-type serovar Typhi. These data indicate that the serovar Typhi LPS core, like the P. aeruginosa LIPS core, is a ligand mediating int ernalization of bacteria by epithelial cells, and that exposure of this lig and on wild-type Typhi is induced by the bacteria's interaction with host c ells.