Mechanisms of. acid resistance due to the urease system of Helicobacter pylori

Background & Aims: Helicobacter pylori, a neutralophile, uses acid neutralization by urease to combat gastric acidity, allowing gastric colonization. Both acute and chronic acid resistance mechanisms are present. Acute mechanisms of acid adaptation could be due to surface urease, increased inner-membrane urea permeability via Urel, or both. Slower mechanisms may involve increased nickel insertion into apoenzyme, posttranscriptional regulation, or increased enzyme synthesis. The aim of this Study was to further define regulation I of urease under acidic conditions. Methods: Surface-bound urease was analyzed by, Measurement of free and bound urease after centrifugation through a step gradient and by quantitative urease immunostaining of intact and fixed bacteria. Changes in urease Synthesis or assembly were determined by incubation Of the organisms at pH 5.5 or 7.0 in the absence and presence of chloramphenicol, urea, or. nickel chelator and in urel-positive and -negative organisms. Results: The amount of surface urease was below detection limits with either centrifugation washing or immunostaining. Total bacterial urease activity was increased 3-5-fold by incubation at pH 5.5 in the presence of chloramphenicol but not in nickel-free medium or in urel knockout organism. There was also a 3-fold increase in survival of acid shock in acid-adapted organisms. Conclusions: Surface-bound urease is too low,to contribute to acid resistance. Acidic medium pH induces Urel-dependent nickel incorporation into apoenzyme. This augmentation of urease activity,increases survival in acid and is part of the gastric colonization strategy of the organism.