title: Frameshift mutations in rdxA and metronidazole resistance in North American Helicobacter pylori isolates.
abstract: In Helicobacter pylori, the oxygen-insensitive nitroreductase RdxA is likely to activate metronidazole (Mtz) by reduction and formation of cytotoxic intermediates. Mutations in rdxA have been associated with Mtz resistance in H. pylori. In vitro Mtz susceptibilities of 17 randomly selected H. pylori isolates were determined by the agar dilution method. DNA sequence analysis of rdxA alleles of eight susceptible isolates (MIC range: 0.25-1.0 mg/L) and nine resistant isolates (MIC range: 16-256 mg/L) showed that six of nine Mtz-resistant H. pylori isolates contained insertion or deletion mutations ('indel' mutations). One isolate contained a substitution mutation at codon position 148 that resulted in the introduction of a premature stop codon. Creation of stop codons within the rdxA coding sequence by either frameshift or substitution mutations resulted in premature translation termination and expression of putatively truncated RdxA polypeptides.
authors.affiliation: Department of Medicine, Baylor College of Medicine, Houston, TX, USA.
authors.forename: D H
authors.initials: DH
authors.lastname: Kwon
authors.forename: J A
authors.initials: JA
authors.lastname: Peña
authors.forename: M S
authors.initials: MS
authors.lastname: Osato
authors.forename: J G
authors.initials: JG
authors.lastname: Fox
authors.forename: D Y
authors.initials: DY
authors.lastname: Graham
authors.forename: J
authors.initials: J
authors.lastname: Versalovic
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000235:genetics*; D018388:Codon, Terminator / Q000235:genetics; D004352:Drug Resistance, Microbial / Q000235:genetics; D016368:Frameshift Mutation / Q000235:genetics*; D016480:Helicobacter pylori / Q000187:drug effects* / Q000201:enzymology / Q000235:genetics; D006801:Humans; D008795:Metronidazole / Q000494:pharmacology*; D009601:Nitroreductases / Q000235:genetics*; D009656:North America; D017422:Sequence Analysis, DNA / Q000379:methods
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D018388:Codon, Terminator; D008795:Metronidazole; D009601:Nitroreductases