The role of the rdxA gene in the evolution of metronidazole resistance in Helicobacter pylori.
It was recently demonstrated that inactivation of the rdxA gene, which encodes an oxygen-insensitive NADPH nitroreductase, is associated with the development of resistance to metronidazole by Helicobacter pylori. In order to further evaluate the contribution of rdxA to metronidazole resistance, the sequence of the rdxA gene was determined for a series of metronidazole-sensitive and -resistant isolates derived from a single, metronidazole-sensitive strain using an H. pylori mouse model. These strains were cultured from the stomachs of mice experimentally infected with H. pylori strain SS1 and then treated orally with metronidazole. The sequence of the rdxA gene of all 10 sequenced metronidazole-sensitive and two (7%) of the 27 metronidazole-resistant isolates was identical to that of the parental strain. In contrast, the rdxA gene of the other 25 metronidazole-resistant isolates contained between one and three frameshift or missense mutations. This suggests that while the development of metronidazole resistance in H. pylori is frequently associated with mutational inactivation of the rdxA gene, other mechanisms of resistance are likely to exist in this bacterium.
Unité de Pathogénie Bactérienne des Muqueuses, Institut Pasteur, Paris, France. pjenks@pasteur.fr
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D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000235:genetics* / Q000502:physiology; D004352:Drug Resistance, Microbial / Q000235:genetics; D019143:Evolution, Molecular; D016480:Helicobacter pylori / Q000187:drug effects* / Q000235:genetics; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics* / Q000502:physiology; D008795:Metronidazole / Q000494:pharmacology*; D020125:Mutation, Missense
D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D008565:Membrane Proteins; D008795:Metronidazole; C077236:RdxA protein, Rhodobacter sphaeroides