Redefinition of the carbohydrate binding specificity of Helicobacter pylori BabA adhesin.

ABSTRACT

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 (Fucα2Galß3(Fucα4)GlcNAc; Le(b)) and the H type 1 determinant (Fucα2Galß3GlcNAc). 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 (Fucα2Galß3GlcNAcß3Galß4Glcß1Cer), Globo H hexaglycosylceramide (Fucα2Galß3GalNAcß3Galα4Galß4Glcß1Cer), and a mixture of three complex glycosphingolipids (Fucα2Galß4GlcNAcß6(Fucα2Galß3GlcNAcß3)Galß3GlcNAcß3Galß4Glcß1Cer, Fucα2Galß3GlcNAcß6(Fucα2Galß3GlcNAcß3)Galß3GlcNAcß3Galß4Glcß1Cer, and Fucα2Galß4(Fucα3)GlcNAcß6(Fucα2Galß3GlcNAcß3)Galß3GlcNAcß3Galß4Glcß1Cer). 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 (GalNAcα3(Fucα2)Galß3GalNAcß3Galα4Galß4Glcß1Cer), i.e. a blood group A determinant 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.