INHIBITION OF HELICOBACTER-PYLORI UREASE BY OMEPRAZOLE

Objectives: To investigate the effect of the proton pump inhibitor omeprazole on the function of purified urease enzyme of Helicobacter pylori and to examine the in vitro activities of omeprazole against urease-positive and -negative Helicobacter strains. Methods: Urease was purified chromatographically from H. pylori. The effect of omeprazole on urease enzyme activity was assayed spectrophotometrically after incubation with urea substrate, phenol red indicator and 3 mmol/l phosphate buffer. Minimal inhibitory concentrations of omeprazole against H. pylori and other Helicobacter species were determined using an agar dilution assay. Results: Omeprazole was found to inhibit the enzyme activity of purified H. pylori urease in a dose-dependent manner. In vitro growth of both urease-positive and mutant urease-negative H. pylori strains was equally inhibited by omeprazole. Conclusions: Whilst omeprazole competitively inhibits the urease enzyme in vitro, urease enzyme inhibition does not account for the in vitro susceptibility of H. pylori to proton pump inhibitors. Urease inhibition by omeprazole in vivo, however, could increase the effectiveness of antibiotics. It may also affect the reliability of the urease-based tests used to assess H. pylori status.