Helicobacter pylori urease suppresses bactericidal activity of peroxynitrite via carbon dioxide production

Hideo Kuwahara, Yoichi Miyamoto, Takaaki Akaike, Tatsuo Kubota, Tomohiro Sawa, Shinichiro Okamoto, Hiroshi Maeda

Research output: Contribution to journalArticlepeer-review

87 Citations (Scopus)

Abstract

Helicobacter pylori can produce a persistent infection in the human stomach, where chronic and active inflammation, including the infiltration of phagocytes such as neutrophils and monocytes, is induced. H. pylori may have a defense system against the antimicrobial actions of phagocytes. We studied the defense mechanism of H. pylori against host-derived peroxynitrite (ONOO- ), a bactericidal metabolite of nitric oxide, focusing on the role of H. pylori urease, which produces CO2 and NH3 from urea and is known to be an essential factor for colonization. The viability of H. pylori decreased in a time-dependent manner with continuous exposure to 1 μM ONOO-, i.e., 0.2% of the initial bacteria remained after a 5-min treatment without urea. The bactericidal action of ONOO- against H. pylori was significantly attenuated by the addition of 10 mM urea, the substrate for urease, whereas ONOO-- induced killing of a urease-deficient mutant of H. pylori or Campylobacter jejuni, another microaerophilic bacterium lacking urease, was not affected by the addition of urea. Such a protective effect of urea was potentiated by supplementation with exogenous urease, and it was almost completely nullified by 10 μM flurofamide, a specific inhibitor of urease. The bactericidal action of ONOO- was also suppressed by the addition of 20 mM NaHCO3 but not by the addition of 20 mM NH3. In addition, the nitration of L-tyrosine of H. pylori after treatment with ONOO- was significantly reduced by the addition of urea or NaHCO3, as assessed by high-performance liquid chromatography with electrochemical detection. These results suggest that H. pylori- associated urease functions to produce a potent ONOO- scavenger, CO2/HCO3-, that defends the bacteria from ONOO- cytotoxicity. The protective effect of urease may thus facilitate sustained bacterial colonization in the infected gastric mucosa.

Original languageEnglish
Pages (from-to)4378-4383
Number of pages6
JournalInfection and immunity
Volume68
Issue number8
DOIs
Publication statusPublished - 2000

ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Immunology
  • Infectious Diseases

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