Urease-mediated destruction of bacteria is specific for Helicobacter urease and results in total cellular disruption

The survival of Helicobacter mustelae, Proteus mirobilis, Escherichia coli and Campylobacter jejuni in the presence of urea and citrate at pH 6.0 was examined. H. mustelae, which has urease activity similar to H. pylori, had a markedly reduced survival, median 2.5% (0-78%) (P < 0.001) when incubated under these conditions. Only 7% of the ammonia produced by H. mustelae urease activity was recovered from the buffer, a similar percentage to that previously reported with H. pylori. None of the other organisms, all of which had lower urease activity, had impaired survival under these conditions. Electron microscopical studies demonstrated extensive structural damage to H. pylori following exposure to urea and citrate at pH 6.0. This structural damage to the organisms makes it unlikely that the low recovery of ammonia was due to retention of ammonia within the bacteria and suggests that the ammonia may have been incorporated into glutamate or other amino acids. Incorporation of ammonia into these compounds would deplete the cell of the key metabolic intermediate alpha-ketoglutarate and could thus explain the mechanism of the urease-dependent destruction of the organism.