title: Helicobacter pylori interacts with the human single-domain trefoil protein TFF1.
abstract: Why Helicobacter pylori colonizes only gastric tissue is unknown. It is found on gastric mucus-secreting cells and in the overlying gastric mucus but not deep in gastric glands. This localization mirrors the expression of trefoil factor 1, TFF1. We hypothesized that H. pylori interacting with TFF1 could explain the tropism of this bacteria for gastric tissue. Recombinant human TFF1 expressed in Escherichia coli was purified by affinity chromatography, ion-exchange chromatography, and gel filtration. Binding of H. pylori was assessed by using flow cytometry and the BIAcore system, which allows real-time monitoring of molecular interactions. In flow cytometry, H. pylori bound to the TFF1 dimer, but Campylobacter jejuni strains and the laboratory strain of E. coli, HB101, did not bind. When the BIAcore system was used, H. pylori bound strongly to TFF1-coated dextran chips compared with uncoated chips. Binding was inhibited by a TFF1 monoclonal antibody and by soluble TFF1. H. pylori bound to porcine gastric mucin only if it was pretreated with TFF1. In conclusion, H. pylori interacts avidly with the dimeric form of TFF1, and this interaction enables binding to gastric mucin, suggesting that TFF1 may act as a receptor for the organism in vivo. This interaction may underline the previously unexplained tropism of this organism for gastric tissue and its colocalization with the gastric mucin MUC5AC.
authors.affiliation: Children's Research Centre, Our Lady's Hospital for Sick Children, Dublin 12, Ireland. marguerite.clyne@ucd.ie
authors.forename: Marguerite
authors.initials: M
authors.lastname: Clyne
authors.forename: Paul
authors.initials: P
authors.lastname: Dillon
authors.forename: Stephen
authors.initials: S
authors.lastname: Daly
authors.forename: Richard
authors.initials: R
authors.lastname: O'Kennedy
authors.forename: Felicity E B
authors.initials: FE
authors.lastname: May
authors.forename: Bruce R
authors.initials: BR
authors.lastname: Westley
authors.forename: Brendan
authors.initials: B
authors.lastname: Drumm
mesh_terms: D019281:Dimerization; D005753:Gastric Mucosa / Q000382:microbiology; D016480:Helicobacter pylori / Q000502:physiology*; D006801:Humans; D007983:Lewis Blood Group Antigens; D011506:Proteins / Q000737:chemistry / Q000378:metabolism*; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D020349:Surface Plasmon Resonance; D000071163:Trefoil Factor-1; D025521:Tumor Suppressor Proteins
chemical_list: D007983:Lewis Blood Group Antigens; D011506:Proteins; D011994:Recombinant Proteins; C051838:TFF1 protein, human; D000071163:Trefoil Factor-1; D025521:Tumor Suppressor Proteins