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

• Published in: International journal of molecular sciences 2019-09, Vol.20 (18), p.4400
• Main Authors: Clyne, Marguerite, May, Felicity E B
• Format: Article
• Language: English
• Subjects: Breast cancer; Chronic infection; Crosslinking; Epithelial cells; Epithelium; Estrogens; Gastric cancer; Gastric Mucins - metabolism; Gastrointestinal system; Gastrointestinal tract; Glucosidases - pharmacology; Granule cells; Helicobacter pylori; Helicobacter pylori - drug effects; Helicobacter pylori - physiology; Humans; Hydrogen-Ion Concentration; Infections; Intestine; lectin; lipopolysacchairde; Lipopolysaccharides - chemistry; Lipopolysaccharides - metabolism; Localization; Mannosidases - pharmacology; MUC5AC; Mucin; Mucin 5AC - metabolism; Mucosa; Mucus; Pancreas; Polysaccharides, Bacterial - chemistry; Polysaccharides, Bacterial - metabolism; Protein Binding - drug effects; Protein Multimerization; Proteins; Review; Stomach; Stomach - microbiology; TFF1; Trefoil factor; Trefoil Factor-1 - chemistry; Trefoil Factor-1 - metabolism; Tropism
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms20184400

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. binds with greater avidity to TFF1 dimer, which is present in gastric mucus, than to TFF1 monomer. Binding of to TFF1 is mediated by the core oligosaccharide subunit of lipopolysaccharide at pH 5.0-6.0. Treatment of lipopolysaccharide with mannosidase or glucosidase inhibits its interaction with TFF1. Both TFF1 and 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-SO . 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 deep in the gastric mucus layer close to the epithelium rather than at the epithelial surface. This restricted localisation could limit the interaction of with epithelial cells and the subsequent host signalling events that promote inflammation.