Lewis X structures in the O antigen side-chain promote adhesion of Helicobacter pylori to the gastric epithelium

Helicobacter pylori NCTC11637 expresses a lipopolysaccharide (LPS) that com prises an O antigen side-chain with structural homology to the human blood group antigen Lewis X (Le(x)). The role of this molecule in adhesion of H. pylori to gastric epithelial cells was investigated. Mutants expressing tru ncated LPS structures were generated through insertional mutagenesis of rfb M and galE; genes encode GDP mannose pyrophosphorylase and galactose epimer ase respectively. Compositional and structural analysis revealed that the g alE mutant expressed a rough LPS that lacked an O antigen side-chain. In co ntrast, an O antigen side-chain was still synthesized by the rfbM mutant, b ut it lacked fucose and no longer reacted with anti-Le(x) monoclonal antibo dies (Mabs). The ability of these mutants to bind to paraffin-embedded sect ions from the antrum region of a human stomach was assessed. Adhesion of th e wild type was characterized by tropic binding to the apical surface of mu cosal epithelial cells and cells lining gastric pits. In contrast, both the rfbM and galE mutants failed to demonstrate tropic binding and adhered to the tissue surface in a haphazard manner. These results indicate that LPS a nd, more specifically, Le(X) structures in the O antigen side-chain play an important role in targeting H. pylori to specific cell lineages within the gastric mucosa. The role of Le(X) in this interaction was confirmed by the tropic binding of synthetic Le(x), conjugated to latex beads, to gastric t issue. The observed pattern of adhesion was indistinguishable from that of wild-type H. pylori.