Clinical isolates of Helicobacter pylori demonstrates alternative BabA-mediated adherence to human gastric mucosa

Helicobacter pylori infection is life-long and can cause peptic ulcer disease and gastric cancer. The H. pylori BabA adhesin binds the ABO/Leb blood group (bg) antigens (Leb), which mediates attachment to the gastric epithelium. The prevalence of ABO binding is high worldwide and also in northern Europe. However, prevalence is reduced by 50% in Germany and is further reduced in Spain and Portugal. An inventory of strains from different European populations resulted in strains with high level of BabA expression but very little or no binding to Leb. The majority of such strains could not bind to human gastric mucosa in vitro. We further characterized a Spanish isolates, strain 812, that binds only weakly to soluble Leb-conjugate but still adheres firmly to gastric mucosa indicative of that it might bind to an alternative set of receptor. Receptor analysis by glycan arrays revealed higher binding of strain 812 to ALeb and Bleb glycans than to Leb, indicating that BabA from strain 812 has shifted its binding epitope somewhat away from the central Fuca1.2Gal bg domain and closer to the very terminal bg A and B determinants, i.e. GalNAca1.3Gal (bgA) or the Gala1.3Gal (bgB). By a colony screening approach we identified a subpopulation of 812 clones adapted for stronger Leb binding. Such affinity shifts comes from replacement of distinguishing amino acids by mechanisms of recombination with a BabA-related outer membrane protein.