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 NeuAcα2–3Gal-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.
Highlights
The gastric pathogen Helicobacter pylori exhibits specific tropism for gastric mucosa in human populations worldwide [1]
Biopsies harvested from the gastric mucosa of humans and experimentally infected Rhesus monkeys were analyzed for spatial localization of H. pylori cells
These results suggest that H. pylori can reach the gastric mucosa capillaries, attach to erythrocytes, and perhaps disseminate throughout the body of both humans and Rhesus monkeys
Summary
The gastric pathogen Helicobacter pylori exhibits specific tropism for gastric mucosa in human populations worldwide [1]. Adherence to gastric epithelium may benefit the bacterium by placing it in close contact with epithelial surfaces and nutrients leaching from host cells that are damaged by local inflammation processes. Binding to highly glycosylated mucins in the mucus layer closest to the epithelium may stabilize H. pylori colonization and avoid clearance of infection caused by high epithelial turnover and shedding of the mucus layer [3]. H. pylori has been shown to adhere to erythrocytes and neutrophils in vitro [4,5], and virulence-associated cagþ H. pylori strains have been shown to invade both the gastric mucosa and individual cells [6,7,8,9,10]. The ability to adhere may affect the outcome of H. pylori infection by facilitating focused delivery of effector molecules into the host cell [11,12]. During infection, tissue invasion and migration of H. pylori bacterial cells through the endothelial lining of capillaries and post-capillary venules followed by adherence to blood cells may result in transfer and systemic dissemination of H. pylori
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