title: 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 (Fucα2Galβ3(Fucα4)GlcNAc; Le(b)) and the H type 1 determinant (Fucα2Galβ3GlcNAc). 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 (Fucα2Galβ3GlcNAcβ3Galβ4Glcβ1Cer), Globo H hexaglycosylceramide (Fucα2Galβ3GalNAcβ3Galα4Galβ4Glcβ1Cer), and a mixture of three complex glycosphingolipids (Fucα2Galβ4GlcNAcβ6(Fucα2Galβ3GlcNAcβ3)Galβ3GlcNAcβ3Galβ4Glcβ1Cer, Fucα2Galβ3GlcNAcβ6(Fucα2Galβ3GlcNAcβ3)Galβ3GlcNAcβ3Galβ4Glcβ1Cer, and Fucα2Galβ4(Fucα3)GlcNAcβ6(Fucα2Galβ3GlcNAcβ3)Galβ3GlcNAcβ3Galβ4Glcβ1Cer). 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)Galβ3GalNAcβ3Galα4Galβ4Glcβ1Cer), 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.
authors: Institute of Biomedicine, Department of Medical Biochemistry and Cell Biology, P. O. Box 440, University of Gothenburg, S-405 30 Göteborg, Sweden.
authors: John
authors: J
authors: Benktander
authors: Jonas
authors: J
authors: Ångström
authors: Michael E
authors: ME
authors: Breimer
authors: Susann
authors: S
authors: Teneberg
mesh_terms: D018829:Adhesins, Bacterial / Q000737:chemistry* / Q000378:metabolism; D000818:Animals; D001422:Bacterial Adhesion; D002240:Carbohydrate Sequence; D002241:Carbohydrates / Q000737:chemistry*; D002853:Chromatography, Liquid; D004848:Epithelium / Q000378:metabolism / Q000382:microbiology; D005753:Gastric Mucosa / Q000378:metabolism / Q000382:microbiology*; D006017:Glycolipids / Q000737:chemistry; D006028:Glycosphingolipids / Q000737:chemistry; D016480:Helicobacter pylori / Q000378:metabolism*; D006801:Humans; D013058:Mass Spectrometry / Q000379:methods; D008969:Molecular Sequence Data; D011485:Protein Binding; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods; D013552:Swine
chemical_list: D018829:Adhesins, Bacterial; C400429:BabA protein, Helicobacter pylori; D002241:Carbohydrates; D006017:Glycolipids; D006028:Glycosphingolipids