THE INFLUENCE OF MICROAEROPHILIA AND ANAEROBIOSIS ON METRONIDAZOLE UPTAKE IN HELICOBACTER-PYLORI

Resistance of Helicobacter pylori to metronidazole during therapy for gastroduodenal ulcers is claimed to be responsible for failure to eradicate the pathogen and thus the disease. Resistance to metronidazole and other nitroimidazoles is rare and documented only for anaerobes; the mechanism of resistance in typical microaerophiles, like Helicobacter, is not known. We have studied metronidazole uptake using high performance liquid chromatography in metronidazole sensitive and resistant strains of H. pylori under conditions of microaerophilia and in anaerobiosis. The uptake of metronidazole was faster in sensitive strains than resistant ones and was also increased in anaerobiosis. Drug uptake and the rate of cell kill was found to be dependent upon the relative oxygen tension of the environment and the cell density, both of which determine the redox conditions of the media. We suggest that resistance displayed in microaerophilia, but which disappears in anaerobiosis, may not involve futile cycling nor the induction of superoxide dismutase and catalase. We further propose that resistant organisms may have alterations in the pattern of pyruvate metabolism as documented for anaerobic bacteria and protozoa and that resistance in microaerophilia may involve the relative efficiencies of detoxifying oxygen in susceptible and resistant strains of H. pylori.