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 enco des an oxygen-insensitive NADPH nitroreductase, is associated with the deve lopment 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-sens itive and -resistant isolates derived from a single, metronidazole-sensitiv e strain using an H. pylori mouse model. These strains were cultured from t he stomachs of mice experimentally infected with H. pylori strain SS1 and t hen 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 contras t, 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 frequent ly associated with mutational inactivation of the rdxA gene, other mechanis ms of resistance are likely to exist in this bacterium.