The Helicobacter pylori Urel protein is essential for survival to acidity and for the first steps of the mouse stomach colonization

Helicobacter pylori (H. pylori) is a Gram negative microaerophilic bacteria whose only known niche is the human gastric mucosa. The presence of H. pyl ori is associated with various pathologies ranging from peptic ulcer diseas e to gastric carcinoma. H. pylori virulence is dependent on its exceptional ability to resist to the stomach acidity by hydrolyzing urea into ammonia. Survival of H. pylori to acidity in the presence of urea relies on the act ivity of a membrane protein, Urel. Aims-We decided to better characterize the role of Urel (i) in vitro in amm onia production through the action of urease, and (ii) in vivo in the colon ization of the gastric mucosa. Methods-Ammonia production by a wild type strain of H. pylori or by a Urel- deficient strain was measured as a function of extracellular pH. In additio n, the kinetics of elimination of a Urel-deficient mutant in vivo were real ized in the mouse model for colonization. Results-Urel was associated with an increase of ammonia production in acidi c conditions in vitro and was necessary for the initial steps of the mouse stomach colonization. Conclusion-Urel thus behaves as a sensor of extracellular pH. This protein activates urease at acidic pH,- thereby, it probably allows H. pylori to re sist to acidity in vivo during the first steps of infection.