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-proteinlinked 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.

The Three-dimensional Structure of the Extracellular Adhesion Domain of the Sialic Acid-binding Adhesin SabA from Helicobacter pylori

“…The physiological significance of this interaction remains to be elucidated. SabA is also essential for binding of H. pylori to sialylated glycoconjugates on erythrocytes and neutrophils (5,7,8). The latter interaction leads to non-opsonic oxidative burst involving G protein signaling and activation of phosphatidylinositol 3-kinase (8).…”

Role ofHelicobacter pyloriinfection in pathogenesis of gastric carcinoma

“…BabA binding to Leb contributes to gene mutations through formation of double stranded DNA breaks in host cell lines [32] . SabA can facilitate colonization in patients lacking Leb by binding to the sialylLewis antigens [33] , and mediate binding of H. pylori to sialylated structures of neutrophils [34] . The data suggest that BabA and SabA might be involved in carcinogenesis as abundance of sialyl-Lewis antigens is commonly enhanced in inflamed or cancerous gastric tissues [35] .…”

Helicobacter pylori—Associated Dyspepsia in Paediatrics

“…The SabA adhesin is the hemagglutinin of H. pylori and allows bacterial adherence to blood cells; this may result in systemic dissemination of the pathogen [55]. Moreover, the binding of SabA to sialic acid carries neutrophil receptors, essential for the nonopsonic activation of human neutrophils [56]. Neutrophils play a major role in the epithelium injury, since these cells have direct toxic effects on the epithelial cells, through the induction of an oxidative burst, with the release of reactive oxygen and nitrogen species.…”