Could frameshift mutations in the frxA and rdxA genes of Helicobacter pylori be a marker for metronidazole resistance

Summary Background Although resistance of Helicobacter pylori to metronidazole had been reported to be associated with mutations in the rdxA or the frxA gene, recent studies have indicated that they may contribute little to metronidazole resistance. Aim To clarify the roles of these genes in metronidazole resistance, we examined them in strains that were not eradicated by first-line eradication therapy. Patients and methods A total of 132 patients (92 males, 40 females, average age: 53.8 years old) who underwent upper gastrointestinal endoscopy after unsuccessful first-line H. pylori eradication were enrolled. Antibiotic susceptibility to metronidazole was investigated using the agar dilution method. The H. pylorirdxA and frxA genes were then sequenced. Results In the metronidazole-resistant strains, the sensitivity of detection of frameshift mutations in the rdxA gene was 44%. A significant association between the presence of frameshift mutations in the rdxA gene and resistance to metronidazole was observed. No significant association between frameshift mutations in the frxA gene and resistance to metronidazole was observed. Conclusion Mutation in the rdxA gene was sufficient, but not necessary to confer resistance to metronidazole in H. pylori. Mutation in the frxA gene was not necessary for resistance to metronidazole in H. pylori.