THE HELICOBACTER-PYLORI UREI PROTEIN IS NOT INVOLVED IN UREASE ACTIVITY BUT IS ESSENTIAL FOR BACTERIAL SURVIVAL IN-VIVO

We produced defined isogenic Helicobacter pylori ureI mutants to inves tigate the function of UreI, the product of one of the genes of the ur ease cluster. The insertion of a cat cassette had a strong polar effec t on the expression of the downstream urease genes, resulting in very weak urease activity, Urease activity, measured in vitro, was normal i n a strain in which ureI was almost completely deleted and replaced wi th a nonpolar cassette. In contrast to previous reports, we thus found that the product of ureI was not necessary for the synthesis of activ e urease. Experiments with the mouse-adapted H. pylori SS1 strain carr ying the nonpolar ureI deletion showed that UreI is essential for H, p ylori survival in vivo and/or colonization of the mouse stomach. The r eplacement of ureI with the nonpolar cassette strongly reduced H. pylo ri survival in acidic conditions (1-h incubation in phosphate-buffered saline solution at pH 2.2) in the presence of 10 mM urea. UreI is pre dicted to be an integral membrane protein and may therefore be involve d int a transport process essential for H, pylori survival in vivo.