title: Mutations in Helicobacter pylori rdxA gene sequences may not contribute to metronidazole resistance.
abstract: Metronidazole resistance in Helicobacter pylori reportedly occurs by mutational inactivation of the oxygen-insensitive nitroreductase gene rdxA. Nucleotide sequences of rdxA were determined in a set of 46 isolates from 19 dyspeptic patients from the UK. The study set comprised matched isolates that were either metronidazole susceptible (four) or mixed metronidazole susceptible and metronidazole resistant (15) before therapy and metronidazole resistant post-therapy (10) in the 11 patients that were followed up. Various mutation types were identified in rdxA of metronidazole-resistant strains (post-treatment) that were absent in matched metronidazole-susceptible strains (pre-treatment). However, rdxA sequences from pre-treatment metronidazole-resistant and metronidazole-susceptible subpopulations were identical in 11 of 15 patients. Thus, mutations in rdxA may not always be essential for metronidazole resistance. Future examination of rdxA expression at the transcription and translational level may provide further insight into the role of this locus in metronidazole action and resistance in H. pylori.
authors.affiliation: Helicobacter Reference Unit, Laboratory of Enteric Pathogens, Central Public Health Laboratory, 61 Colindale Avenue, Colindale, London NW9 5HT, UK. schisholm@phls.nhs.uk
authors.forename: Stephanie A
authors.initials: SA
authors.lastname: Chisholm
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Owen
mesh_terms: D004269:DNA, Bacterial / Q000235:genetics / Q000302:isolation & purification; D024881:Drug Resistance, Bacterial; D005798:Genes, Bacterial; D005838:Genotype; D016481:Helicobacter Infections / Q000382:microbiology; D016480:Helicobacter pylori / Q000187:drug effects*; D006801:Humans; D008795:Metronidazole / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D009154:Mutation / Q000235:genetics*; D009601:Nitroreductases / Q000235:genetics*; D012150:Polymorphism, Restriction Fragment Length; D013270:Stomach / Q000382:microbiology
chemical_list: D004269:DNA, Bacterial; D008795:Metronidazole; C029492:aromatic NADH-dependent nitroreductase; D009601:Nitroreductases