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.

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Cited by papers we hold 7

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• Sialic acid catabolism drives intestinal inflammation and microbial dysbiosis in mice · 2015
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• Virulence Factors of A Review · 2014
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• The Role of Helicobacter pylori Outer Membrane Proteins in Adherence and Pathogenesis · 2013
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• Molecular mechanisms of gastric epithelial cell adhesion and injection of CagA by Helicobacter pylori · 2011
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• Biochemical and functional characterization of Helicobacter pylori vesicles · 2010
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• Role of ABO Secretor Status in Mucosal Innate Immunity and H. pylori Infection · 2008
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