The Interaction of Helicobacter pylori with TFF1 and Its Role in Mediating the Tropism of the Bacteria Within the Stomach.

Marguerite Clyne,Felicity E B May

doi:10.3390/ijms20184400

Marguerite Clyne, Felicity E B May

Open Access

https://doi.org/10.3390/ijms20184400

Copy DOI

Abstract

Helicobacter pylori colonises the human stomach and has tropism for the gastric mucin, MUC5AC. The majority of organisms live in the adherent mucus layer within their preferred location, close to the epithelial surface where the pH is near neutral. Trefoil factor 1 (TFF1) is a small trefoil protein co-expressed with the gastric mucin MUC5AC in surface foveolar cells and co-secreted with MUC5AC into gastric mucus. Helicobacter pylori binds with greater avidity to TFF1 dimer, which is present in gastric mucus, than to TFF1 monomer. Binding of H. pylori to TFF1 is mediated by the core oligosaccharide subunit of H. pylori lipopolysaccharide at pH 5.0–6.0. Treatment of H. pylori lipopolysaccharide with mannosidase or glucosidase inhibits its interaction with TFF1. Both TFF1 and H. pylori have a propensity for binding to mucins with terminal non-reducing α- or β-linked N-acetyl-d-glucosamine or α-(2,3) linked sialic acid or Gal-3-SO42−. These findings are strong evidence that TFF1 has carbohydrate-binding properties that may involve a conserved patch of aromatic hydrophobic residues on the surface of its trefoil domain. The pH-dependent lectin properties of TFF1 may serve to locate H. pylori deep in the gastric mucus layer close to the epithelium rather than at the epithelial surface. This restricted localisation could limit the interaction of H. pylori with epithelial cells and the subsequent host signalling events that promote inflammation.

Highlights

Helicobacter pylori has been shown to colocalise with the mucin MUC5AC that is secreted by normal gastric surface mucosal cells [15,16]
60% of the global human population is infected with Helicobacter pylori which means that H. pylori is one of the commonest pathogens of mankind
Helicobacter pylori is classed as a group I carcinogen because infection is associated with the development of gastric cancer [6,7] of which the vast majority of cases are of non-cardia gastric cancer [8]

Summary

Introduction

Helicobacter pylori has been shown to colocalise with the mucin MUC5AC that is secreted by normal gastric surface mucosal cells [15,16]. Three molecular forms of TFF1 were detected in normal gastric mucosa and adherent mucus, a 6.67 kDa monomer, a 13.33 kDa homodimer and an ~25 kDa heterodimer [45] with another secreted protein, the 18.3 kDa TFIZ1 [46] encoded by GKN2 [47].

Results

Conclusion