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

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.

TFF1 Induces Aggregation and Reduces Motility of Helicobacter pylori

“…We corroborated the existence of this interaction, also demonstrating that H. felis, another species of the Helicobacteraceae family, was not able to bind the TFF1 protein. This additional result is in line with the hypothesis that H. pylori co-evolved with its host for at least 100,000 years [30], and suggests that the interaction between TFF1 and H. pylori could have a role not only mediating the tropism of the bacterium within the stomach [31], but also affecting the fitness of H. pylori in different human hosts and explaining the frequent asymptomatic persistence.…”

Molecular Alterations in the Stomach of Tff1-Deficient Mice: Early Steps in Antral Carcinogenesis

“…In the past, homodimeric TFF1 has also been demonstrated to act as a lectin, e.g., it interacts with a lipopolysaccharide of Helicobacter pylori in a pH-dependent manner [28]. Thus, TFF1 may have a role in mediating the tropism of H. pylori within the gastric mucus [29].…”

The Tumor Suppressor TFF1 Occurs in Different Forms and Interacts with Multiple Partners in the Human Gastric Mucus Barrier: Indications for Diverse Protective Functions

“…Furthermore, homodimeric TFF1 has lectin activities enabling pH-dependent binding to a lipopolysaccharide of Helicobacter pylori [29]. This led to the hypothesis that TFF1 plays a role in mediating the tropism of H. pylori within the gastric mucus [30].…”