Human Gastric Mucins Differently Regulate Helicobacter pylori Proliferation, Gene Expression and Interactions with Host Cells

Abstract

Helicobacter pylori colonizes the mucus niche of the gastric mucosa and is a risk factor for gastritis, ulcers and cancer. The main components of the mucus layer are heavily glycosylated mucins, to which H. pylori can adhere. Mucin glycosylation differs between individuals and changes during disease. Here we have examined the H. pylori response to purified mucins from a range of tumor and normal human gastric tissue samples. Our results demonstrate that mucins from different individuals differ in how they modulate both proliferation and gene expression of H. pylori. The mucin effect on proliferation varied significantly between samples, and ranged from stimulatory to inhibitory, depending on the type of mucins and the ability of the mucins to bind to H. pylori. Tumor-derived mucins and mucins from the surface mucosa had potential to stimulate proliferation, while gland-derived mucins tended to inhibit proliferation and mucins from healthy uninfected individuals showed little effect. Artificial glycoconjugates containing H. pylori ligands also modulated H. pylori proliferation, albeit to a lesser degree than human mucins. Expression of genes important for the pathogenicity of H. pylori (babA, sabA, cagA, flaA and ureA) appeared co-regulated in response to mucins. The addition of mucins to co-cultures of H. pylori and gastric epithelial cells protected the viability of the cells and modulated the cytokine production in a manner that differed between individuals, was partially dependent of adhesion of H. pylori to the gastric cells, but also revealed that other mucin factors in addition to adhesion are important for H. pylori-induced host signaling. The combined data reveal host-specific effects on proliferation, gene expression and virulence of H. pylori due to the gastric mucin environment, demonstrating a dynamic interplay between the bacterium and its host.

Divergence between the Highly Virulent Zoonotic Pathogen Helicobacter heilmannii and Its Closest Relative, the Low-Virulence “Helicobacter ailurogastricus” sp. nov

“…In the present study, however, the in vitro capacities of H. heilmannii and H. ailurogastricus for binding to human gastric mucins were very low, and there was no difference in binding at low or neutral pHs. The binding capacities of H. heilmannii and H. ailurogastricus were 20-to 100-fold lower than the capacity of H. pylori for binding to the same human gastric mucins (42,52,54). Mucins can carry on the order of 100 different carbohydrate structures, which provide the mucins with a bottle brush appearance and make them act as receptors for microorganisms (55).…”

Divergent Mechanisms of Interaction of Helicobacter pylori and Campylobacter jejuni with Mucus and Mucins

“…This suggests that either the mucus layer on HT29-MTX-E12 cells offered additional H. pylori receptors not present on the other cell lines or the mucus induced an alteration in adhesins produced by the organism that enabled interaction with the cells. Gastric mucins have been shown to promote the proliferation of H. pylori and to alter gene expression by the organism (58). Recently, we have shown that the interaction of H. pylori with the trefoil peptide TFF1, present in the adherent mucus layer of HT29-MTX E12 cells, promotes infection (21).…”

Aeromonas salmonicida Growth in Response to Atlantic Salmon Mucins Differs between Epithelial Sites, Is Governed by Sialylated and N -Acetylhexosamine-Containing O -Glycans, and Is Affected by Ca 2+

“…Mucins can bind pathogens and can modulate bacterial growth, e.g., via stimulatory or inhibitory glycan motifs (17,18) and/or by being food sources for bacteria through released glycans (19). The ability of the mucin glycan structures to bind bacteria plays an important role in the mucosal defense against infection (15,20).…”