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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 (Fuc?2Gal?3(Fuc?4)GlcNAc; Le(b)) and the H type 1 determinant (Fuc?2Gal?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?2Gal?3GlcNAc?3Gal?4Glc?1Cer), Globo H hexaglycosylceramide (Fuc?2Gal?3GalNAc?3Gal?4Gal?4Glc?1Cer), and a mixture of three complex glycosphingolipids (Fuc?2Gal?4GlcNAc?6(Fuc?2Gal?3GlcNAc?3)Gal?3GlcNAc?3Gal?4Glc?1Cer, Fuc?2Gal?3GlcNAc?6(Fuc?2Gal?3GlcNAc?3)Gal?3GlcNAc?3Gal?4Glc?1Cer, and Fuc?2Gal?4(Fuc?3)GlcNAc?6(Fuc?2Gal?3GlcNAc?3)Gal?3GlcNAc?3Gal?4Glc?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?3(Fuc?2)Gal?3GalNAc?3Gal?4Gal?4Glc?1Cer), 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.

SUBMITTER: Benktander J

PROVIDER: S-EPMC3442506 | biostudies-literature | 2012 Sep

REPOSITORIES: biostudies-literature

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

Benktander John J Ångström Jonas J Breimer Michael E ME Teneberg Susann S

The Journal of biological chemistry 20120720 38

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 ...[more]

PMID: 22822069

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Project description:UNLABELLED:Helicobacter pylori undergoes rapid microevolution during chronic infection, but very little is known about how this affects host interaction factors. The best-studied adhesin of H. pylori is BabA, which mediates binding to the blood group antigen Lewis b [Le(b)]. To study the dynamics of Le(b) adherence during human infection, we analyzed paired H. pylori isolates obtained sequentially from chronically infected individuals. A complete loss or significant reduction of Le(b) binding was observed in strains from 5 out of 23 individuals, indicating that the Le(b) binding phenotype is quite stable during chronic human infection. Sequence comparisons of babA identified differences due to mutation and/or recombination in 12 out of 16 strain pairs analyzed. Most amino acid changes were found in the putative N-terminal extracellular adhesion domain. One strain pair that had changed from a Le(b) binding to a nonbinding phenotype was used to study the role of distinct sequence changes in Le(b) binding. By transformations of the nonbinding strain with a babA gene amplified from the binding strain, H. pylori strains with mosaic babA genes were generated. Recombinants were enriched for a gain of Le(b) binding by biopanning or for BabA expression on the bacterial surface by pulldown assay. With this approach, we identified several amino acid residues affecting the strength of Le(b) binding. Additionally, the data showed that the C terminus of BabA, which is predicted to encode an outer membrane ?-barrel domain, plays an essential role in the biogenesis of this protein. IMPORTANCE:Helicobacter pylori causes a chronic infection of the human stomach that can lead to ulcers and cancer. The bacterium can bind to gastric epithelial cells with specialized outer membrane proteins. The best-studied protein is the BabA adhesin which binds to the Lewis b blood group antigen. Since H. pylori is a bacterium with very high genetic variability, we asked whether babA evolves during chronic infection and how mutations or recombination in babA affect binding. We found that BabA-mediated adherence was stable in most individuals but observed a complete loss of binding or reduced binding in 22% of individuals. One strain pair in which binding was lost was used to generate babA sequences that were mosaics of a functional allele and a nonfunctional allele, and the mosaic sequences were used to identify amino acids critically involved in binding of BabA to Lewis b.

Dataset Information

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

Publications

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

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