title: The sialic acid binding SabA adhesin of Helicobacter pylori is essential for nonopsonic activation of human neutrophils.
abstract: Infiltration of neutrophils and monocytes into the gastric mucosa is a hallmark of chronic gastritis caused by Helicobacter pylori. Certain H. pylori strains nonopsonized stimulate neutrophils to production of reactive oxygen species causing oxidative damage of the gastric epithelium. Here, the contribution of some H. pylori virulence factors, the blood group antigen-binding adhesin BabA, the sialic acid-binding adhesin SabA, the neutrophil-activating protein HP-NAP, and the vacuolating cytotoxin VacA, to the activation of human neutrophils in terms of adherence, phagocytosis, and oxidative burst was investigated. Neutrophils were challenged with wild type bacteria and isogenic mutants lacking BabA, SabA, HP-NAP, or VacA. Mutant and wild type strains lacking SabA had no neutrophil-activating capacity, demonstrating that binding of H. pylori to sialylated neutrophil receptors plays a pivotal initial role in the adherence and phagocytosis of the bacteria and the induction of the oxidative burst. The link between receptor binding and oxidative burst involves a G-protein-linked signaling pathway and downstream activation of phosphatidylinositol 3-kinase as shown by experiments using signal transduction inhibitors. Collectively our data suggest that the sialic acid-binding SabA adhesin is a prerequisite for the nonopsonic activation of human neutrophils and, thus, is a virulence factor important for the pathogenesis of H. pylori infection.
authors.affiliation: Department of Clinical Microbiology, Orebro University Hospital.
authors.forename: Magnus
authors.initials: M
authors.lastname: Unemo
authors.forename: Marina
authors.initials: M
authors.lastname: Aspholm-Hurtig
authors.forename: Dag
authors.initials: D
authors.lastname: Ilver
authors.forename: Jörgen
authors.initials: J
authors.lastname: Bergström
authors.forename: Thomas
authors.initials: T
authors.lastname: Borén
authors.forename: Dan
authors.initials: D
authors.lastname: Danielsson
authors.forename: Susann
authors.initials: S
authors.lastname: Teneberg
mesh_terms: D018829:Adhesins, Bacterial / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*; D000818:Animals; D001422:Bacterial Adhesion; D001426:Bacterial Proteins / Q000737:chemistry; D002851:Chromatography, High Pressure Liquid; D002855:Chromatography, Thin Layer; D003603:Cytotoxins / Q000737:chemistry; D004591:Electrophoresis, Polyacrylamide Gel; D006098:Granulocytes / Q000378:metabolism; D016480:Helicobacter pylori / Q000378:metabolism*; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D009682:Magnetic Resonance Spectroscopy; D019158:N-Acetylneuraminic Acid / Q000378:metabolism*; D009504:Neutrophils / Q000737:chemistry / Q000378:metabolism* / Q000382:microbiology*; D009841:Oligonucleotides / Q000737:chemistry; D018384:Oxidative Stress; D010587:Phagocytosis; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D011485:Protein Binding; D017382:Reactive Oxygen Species; D016897:Respiratory Burst; D015398:Signal Transduction; D013997:Time Factors
chemical_list: D018829:Adhesins, Bacterial; D001426:Bacterial Proteins; D003603:Cytotoxins; D006861:Hydrogen Peroxide; D019158:N-Acetylneuraminic Acid; D009841:Oligonucleotides; D019869:Phosphatidylinositol 3-Kinases; D017382:Reactive Oxygen Species; C400429:BabA protein, Helicobacter pylori; C500808:SabA protein, Helicobacter pylori; C092412:neutrophil-activating protein A, Helicobacter pylori