TFF1 induces aggregation of Helicobacter pylori and slows-down its motility

ELETTO, DANIELA; FÁTIMA MARIA MENTUCCI; VLLAHU, MEGI; PORTA, AMALIA; TOSCO, ALESSANDRA

Congreso; 16th SIBBM Seminar .Frontiers in Molecular Biology. Frontiers in metabolic research; 2021

Helicobacter pylori is a gram-negative bacterium colonizing the gastric mucosa of half of theworld’s population and is the first formally recognized bacterial carcinogen. The gastricmucous plays a key role in the defense after injury due to bacterial infection, secretingvarious factors, including TFF1. This is a mucin-associated protective factor, and it has beenproposed as a gastric tumor suppressor gene. A strong relationship between H. pylori andTFF1 has been reported in the literature. In particular, H. pylori interacts with the dimericform of TFF1 and its expression is induced in infected cellular models, but down-regulated inchronic infected patients. The protective role of TFF1 is well documented, however there arenot currently studies about the molecular mechanisms that confer a beneficial function to theinteraction between TFF1 and H. pylori. We hypothesize that TFF1 blocks H. pylori in themucus slowing down its migration towards the epithelial layer and therefore preventingexcessive H. pylori colonization. By pull-down assays we assessed the existence of a specificinteraction between human TFF1 and H. pylori, but not with H. felis. Moreover, wedemonstrated that the gastrointestinal peptide induces H. pylori aggregation in aconcentration dependent manner, and forces the bacterium to undergo a morphologicaltransformation from a spiral to a filamentous shape without affecting bacterium proliferation.TFF1 has no chemotactic effect on H. pylori, but reduces bacterial motility probably byinducing its aggregation. Two genes encoding a component of the flagellum (flgE and flaB)and a virulence gene encoding a component of the secretory apparatus complex virB/D, weretranscriptionally downregulated and this is consistent with the compromised motility. Finally,our results suggest that the interaction between TFF1 and the bacterium may explain thefrequent persistence of H. pylori in human host without inducing disease.