Genetic and functional characterization of the alpAB gene locus essential for the adhesion of Helicobacter pylori to human gastric tissue

In this study, we isolated and characterized a chromosomal locus of Helicob acter pylori previously identified by transposon shuttle mutagenesis as bei ng involved in the adhesion of the pathogen to gastric epithelial cells, Tw o closely homologous genes were identified, designated as alpA and alpB, en coding outer membrane (OM) proteins of 518 amino acids each. They are membe rs of the outer membrane protein supergene family identified in the H. pylo ri 26695 complete genome sequence, AlpA carries a functional lipoprotein si gnal sequence. AlpB carries a putative standard N-terminal signal sequence and shows a strong amino-acid sequence identity to AlpA. Transposon inserti on mutagenesis, immunoblotting and primer extension studies indicate that b oth genes are organized in an operon, but no obvious consensus promoter seq uence was found upstream of the transcriptional start site. The C-terminal portion of both proteins is predicted to form a porin-like beta-barrel in t he outer membrane, consisting of 14 transmembrane amphipathic beta-strands. Adhesion experiments with defined isogenic mutants indicate that both prot eins are necessary for specific adherence of H. pylori to human gastric tis sue. The pattern of AlpAB-dependent adherence of H. pylori to the gastric e pithelial surface shows a clear difference to the BabA2-mediated adherence to Lewis(b), suggesting that a different receptor is involved.