© 2003 by BMJ Publishing Group & British Society of Gastroenterology
HELICOBACTER PYLORI
Aspirin inhibits the growth of Helicobacter pylori and enhances its susceptibility to antimicrobial agents
1 Department of Gastroenterology, First Hospital, Peking University, Beijing, China
2 Department of Medicine, University of Hong Kong, Hong Kong, China
3 Department of Molecular Microbiology, Washington University Medical School, St Louis, Missouri 63110, USA
Correspondence to:
Correspondence to:
Dr B C Y Wong, Department of Medicine, University of Hong Kong, Queen Mary Hospital, Hong Kong, China;
bcywong{at}hku.hk
Background and aim: The role of Helicobacter pylori and aspirin in peptic ulcer formation and recurrence remains an important clinical topic. The interaction between aspirin and H pylori in vitro is also not clear. We investigated the effect of aspirin on the growth of H pylori and on the susceptibility of H pylori to antimicrobials.
Methods: Time killing studies of H pylori were performed with different concentrations of aspirin and salicylate. Growth of bacteria was assessed spectrophotometrically and by viable colony count. The effects of aspirin on the efficiency of colony formation and on metronidazole induced mutation to rifampicin resistance in H pylori were determined. Minimal inhibitory concentrations (MICs) of aspirin and metronidazole were tested by the standard agar dilution method. MICs of amoxycillin and clarithromycin were determined by the E test method.
Results: Aspirin and salicylate inhibited the growth of H pylori in a dose dependent manner and bactericidal activity was due to cell lysis. Aspirin 400 µg/ml caused a 2 logs decrease in colony forming units/ml at 48 hours, and suppressed the normal ability of metronidazole to induce new mutations to rifampicin. The IC90 of aspirin was 512 µg/ml. Increased susceptibility of amoxycillin, clarithromycin, and metronidazole to H pylori was observed at 1 mM (180 µg/ml) aspirin.
Conclusions: Aspirin inhibited the growth of H pylori, suppressed the mutagenic effect of metronidazole, and enhanced the susceptibility of H pylori to antimicrobial agents. This mechanism is important in future drug development for effective clearing and overcoming resistance.
Keywords: Helicobacter pylori; aspirin; mutagenesis; resistance; antimicrobials
Abbreviations: MIC, minimal inhibitory concentration; NSAID, non-steroidal anti-inflammatory drug; MtzS, metronidazole susceptible; MtzR, metronidazole resistance; BHI, brain heart infusion; FBS, fetal bovine serum; DMSO, dimethylsulphoxide; CFU, colony forming unit; RifR, rifampicin resistance
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Gut 2003 52: 459.
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