Redefinition of the Carbohydrate Binding Specificity of Helicobacter pylori BabA Adhesin

Certain Helicobacter pylori strains adhere to the human gastric epithelium using the blood group antigen-binding adhesin (BabA). All BabA-expressing H. pylori strains bind to the blood group O determinants on type 1 core chains, i.e. to the Lewis b antigen (Fuc alpha 2Gal beta 3(Fuc alpha 4) GlcNAc; Le(b)) and the H type 1 determinant (Fuc alpha 2Gal beta 3GlcNAc). Recently, BabA strains have been categorized into those recognizing only Le(b) and H type 1 determinants (designated specialist strains) and those that also bind to A and B type 1 determinants (designated generalist strains). Here, the structural requirements for carbohydrate recognition by generalist and specialist BabA were further explored by binding of these types of strains to a panel of different glycosphingolipids. Three glycosphingolipids recognized by both specialist and generalist BabA were isolated from the small intestine of a blood group O pig and characterized by mass spectrometry and proton NMR as H type 1 pentaglycosylceramide (Fuc alpha 2Gal beta 3GlcNAc beta 3Gal beta 4Glc beta 1Cer), Globo H hexaglycosylceramide (Fuc alpha 2Gal beta 3GalNAc beta 3Gal alpha 4Gal beta 4Glc beta 1Cer), and a mixture of three complex glycosphingolipids (Fuc alpha 2Gal beta 4GlcNAc beta 6(Fuc alpha 2Gal beta 3GlcNAc beta 3)Gal beta 3GlcNAc beta 3Gal beta 4Glc beta 1Cer, Fuc alpha 2Gal beta 3GlcNAc beta 6(Fuc alpha 2Gal beta 3GlcNAc beta 3)Gal beta 3GlcNAc beta 3Gal beta 4Glc beta 1Cer, and Fuc alpha 2Gal beta 4(Fuc alpha 3)GlcNAc beta 6(Fuc alpha 2Gal beta 3GlcNAc beta 3)Gal beta 3GlcNAc beta 3Gal beta 4Glc beta 1Cer). In addition to the binding of both strains to the Globo H hexaglycosylceramide, i.e. a blood group O determinant on a type 4 core chain, the generalist strain bound to the Globo A heptaglycosylceramide (GalNAc alpha 3(Fuc alpha 2)Gal beta 3GalNAc beta 3Gal alpha 4Gal beta 4Glc beta 1Cer), i.e. a blood groupAdeterminant on a type 4 core chain. The binding of BabA to the two sets of isoreceptors is due to conformational similarities of the terminal disaccharides of H type 1 and Globo H and of the terminal trisaccharides of A type 1 and Globo A.