Lewis X structures in the O antigen side‐chain promote adhesion of <i>Helicobacter pylori</i> to the gastric epithelium

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<jats:p> <jats:italic>Helicobacter pylori</jats:italic> NCTC11637 expresses a lipopolysaccharide (LPS) that comprises an O antigen side‐chain with structural homology to the human blood group antigen Lewis X (Le<jats:sup>x</jats:sup>). The role of this molecule in adhesion of <jats:italic>H. pylori</jats:italic> to gastric epithelial cells was investigated. Mutants expressing truncated LPS structures were generated through insertional mutagenesis of <jats:italic>rfbM</jats:italic> and <jats:italic>galE;</jats:italic> genes encode GDP mannose pyrophosphorylase and galactose epimerase respectively. Compositional and structural analysis revealed that the <jats:italic>galE</jats:italic> mutant expressed a rough LPS that lacked an O antigen side‐chain. In contrast, an O antigen side‐chain was still synthesized by the <jats:italic>rfbM</jats:italic> mutant, but it lacked fucose and no longer reacted with anti‐Le<jats:sup>x</jats:sup> monoclonal antibodies (Mabs). The ability of these mutants to bind to paraffin‐embedded sections from the antrum region of a human stomach was assessed. Adhesion of the wild type was characterized by tropic binding to the apical surface of mucosal epithelial cells and cells lining gastric pits. In contrast, both the <jats:italic>rfbM</jats:italic> and <jats:italic>galE</jats:italic> mutants failed to demonstrate tropic binding and adhered to the tissue surface in a haphazard manner. These results indicate that LPS and, more specifically, Le<jats:sup>X</jats:sup> structures in the O antigen side‐chain play an important role in targeting <jats:italic>H. pylori</jats:italic> to specific cell lineages within the gastric mucosa. The role of Le<jats:sup>X</jats:sup> in this interaction was confirmed by the tropic binding of synthetic Le<jats:sup>x</jats:sup>, conjugated to latex beads, to gastric tissue. The observed pattern of adhesion was indistinguishable from that of wild‐type <jats:italic>H. pylori</jats:italic>.</jats:p>

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