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, ionexchange 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.

The trefoil factor family – small peptides with multiple functionalities

“…Moreover, expression of the TFFs is increased during infection with H. pylori, which seems contradictory to the role of TFF1 in protecting and restituting the mucosa [228,229]. In addition, GKN2 is downregulated during infection with H. pylori [227], which may lead to even more TFF1 ready for interaction with the bacteria.…”

“…Interestingly, another study showed that Helicobacter pylori bound specifically and with high avidity to dimeric TFF1. This binding was necessary for binding of the bacteria to MUC5AC and thus for their selective colonization of the gastric mucosal surface [227]. Moreover, expression of the TFFs is increased during infection with H. pylori, which seems contradictory to the role of TFF1 in protecting and restituting the mucosa [228,229].…”

Helicobacter Pylori: Current Status and Future Prospects

“…Another potential inhibitor has been investigated by Bai et al 30 An analogue of BabA, known as recombinant BabA (rBabA), was found to partially inhibit binding of H. pylori to gastric epithelial cells and significantly inhibit adhesion to the gastric cancer cell line MGC-803. If indeed TFF1 is a receptor for H. pylori in the human stomach, as suggested by Clyne et al 22 , then their studies have also demonstrated a potential anti-adhesion therapy. They found that adhesion of H. pylori to TFF1-dimer coated beads was inhibited by either pre-incubating the bacteria with soluble recombinant TFF1 or by pre-incubating the beads with anti-TFF1 monoclonal antibody.…”

“…In the gastrointestinal epithelium, TFF proteins are expressed in a site-specific manner, TFF1 being primarily located within the foveolar pit cells of the gastric body and superficial regions of the antral glands 21 . Studies by Clyne et al 22 have shown that H. pylori is able to bind to TFF1, suggesting that alongside Le b, TFF1 may also be a receptor for H. pylori in vivo and may provide another reason for its tropism for gastric tissue.…”

Trefoil factors

“…More recently, it has also been shown that TFF2 messenger RNA (mRNA) levels increase within minutes following gastric ulceration in rats [74], and TFF2-defi cient mice present a larger number of non steroidal anti-infl ammatory drug (NSAID)-induced ulcers when compared with wild-type animals [66]. Another interesting possibility results from the demonstration that TFF1 overexpression can confer on Helicobacter pylori an enhanced ability to colonize the gastric mucosa [75]. H. pylori infection fi rst induces chronic superfi cial (non-atrophic) gastritis, which can progress through chronic atrophic gastritis, intestinal metaplasia and dysplasia toward gastric cancer [76,77].…”