Acidic media trigger cytoplasmic urease activity of the unique human gastri
c pathogen Helicobacter pylori. Deletion of urel prevents this activation o
f cytoplasmic urease that is essential for bacterial acid resistance. Urel
is an inner membrane protein with six transmembrane segments as shown by in
vitro transcription/translation and membrane separation. Expression of Ure
l in Xenopus oocytes results in acid-stimulated urea uptake, with a pH prof
ile similar to activation of cytoplasmic urease, Mutation of periplasmic hi
stidine 123 abolishes stimulation. Urel-mediated transport is urea specific
, passive, nonsaturable, nonelectrogenic, and temperature independent. Urel
functions as a H+-gated urea channel regulating cytoplasmic urease that is
essential for gastric survival and colonization.