Structural Insights into Polymorphic ABO Glycan Binding by Helicobacter pylori

The Helicobacter pylori adhesin BabA binds mucosal ABO/Leb blood group carbohydrates. The adhesin facilitates bacterial attachment to gastric surfaces, increasing strain virulence and forming a recognized risk factor for peptic ulcers and gastric cancer. High sequence variation causes BabA functional diversity, but the underlying structural-molecular determinants are unknown.

The X-ray structures of representative BabA isoforms revealed a polymorphic, three-pronged Leb binding site. The anchor point for receptor binding is the embrace of an ABO fucose residue by a disulfide-clasped loop, which is inactivated by reduction. Treatment with the redoxactive pharmaceutic N-acetylcysteine lowers gastric mucosal neutrophil infiltration in Helicobacter pylori-infected Leb-expressing mice, providing perspectives on possible Helicobacter pylori eradication therapies.