title: SabA is the H. pylori hemagglutinin and is polymorphic in binding to sialylated glycans.
abstract: Adherence of Helicobacter pylori to inflamed gastric mucosa is dependent on the sialic acid-binding adhesin (SabA) and cognate sialylated/fucosylated glycans on the host cell surface. By in situ hybridization, H. pylori bacteria were observed in close association with erythrocytes in capillaries and post-capillary venules of the lamina propria of gastric mucosa in both infected humans and Rhesus monkeys. In vivo adherence of H. pylori to erythrocytes may require molecular mechanisms similar to the sialic acid-dependent in vitro agglutination of erythrocytes (i.e., sialic acid-dependent hemagglutination). In this context, the SabA adhesin was identified as the sialic acid-dependent hemagglutinin based on sialidase-sensitive hemagglutination, binding assays with sialylated glycoconjugates, and analysis of a series of isogenic sabA deletion mutants. The topographic presentation of binding sites for SabA on the erythrocyte membrane was mapped to gangliosides with extended core chains. However, receptor mapping revealed that the NeuAcalpha2-3Gal-disaccharide constitutes the minimal sialylated binding epitope required for SabA binding. Furthermore, clinical isolates demonstrated polymorphism in sialyl binding and complementation analysis of sabA mutants demonstrated that polymorphism in sialyl binding is an inherent property of the SabA protein itself. Gastric inflammation is associated with periodic changes in the composition of mucosal sialylation patterns. We suggest that dynamic adaptation in sialyl-binding properties during persistent infection specializes H. pylori both for individual variation in mucosal glycosylation and tropism for local areas of inflamed and/or dysplastic tissue.
authors.affiliation: Department of Odontology, Section of Oral Microbiology, Umeå University, Umeå, Sweden.
authors.forename: Marina
authors.initials: M
authors.lastname: Aspholm
authors.forename: Farzad O
authors.initials: FO
authors.lastname: Olfat
authors.forename: Jenny
authors.initials: J
authors.lastname: Nordén
authors.forename: Berit
authors.initials: B
authors.lastname: Sondén
authors.forename: Carina
authors.initials: C
authors.lastname: Lundberg
authors.forename: Rolf
authors.initials: R
authors.lastname: Sjöström
authors.forename: Siiri
authors.initials: S
authors.lastname: Altraja
authors.forename: Stefan
authors.initials: S
authors.lastname: Odenbreit
authors.forename: Rainer
authors.initials: R
authors.lastname: Haas
authors.forename: Torkel
authors.initials: T
authors.lastname: Wadström
authors.forename: Lars
authors.initials: L
authors.lastname: Engstrand
authors.forename: Cristina
authors.initials: C
authors.lastname: Semino-Mora
authors.forename: Hui
authors.initials: H
authors.lastname: Liu
authors.forename: André
authors.initials: A
authors.lastname: Dubois
authors.forename: Susann
authors.initials: S
authors.lastname: Teneberg
authors.forename: Anna
authors.initials: A
authors.lastname: Arnqvist
authors.forename: Thomas
authors.initials: T
authors.lastname: Borén
mesh_terms: D018829:Adhesins, Bacterial / Q000235:genetics / Q000378:metabolism*; D000327:Adsorption; D000818:Animals; D000942:Antigens, Bacterial / Q000378:metabolism; D001422:Bacterial Adhesion; D001665:Binding Sites; D001667:Binding, Competitive; D002196:Capillaries; D004912:Erythrocytes / Q000378:metabolism / Q000382:microbiology; D005732:Gangliosides / Q000378:metabolism; D005753:Gastric Mucosa / Q000098:blood supply / Q000382:microbiology; D017353:Gene Deletion; D016481:Helicobacter Infections / Q000276:immunology / Q000382:microbiology; D016480:Helicobacter pylori / Q000378:metabolism / Q000502:physiology*; D006384:Hemagglutination; D006388:Hemagglutinins / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D008253:Macaca mulatta; D019158:N-Acetylneuraminic Acid / Q000378:metabolism*; D009844:Oligosaccharides / Q000378:metabolism; D011134:Polysaccharides / Q000378:metabolism*; D000080506:Sialyl Lewis X Antigen; D014699:Venules
chemical_list: D018829:Adhesins, Bacterial; D000942:Antigens, Bacterial; D005732:Gangliosides; D006388:Hemagglutinins; D009844:Oligosaccharides; D011134:Polysaccharides; C500808:SabA protein, Helicobacter pylori; D000080506:Sialyl Lewis X Antigen; D019158:N-Acetylneuraminic Acid