title: Genetic analysis of Helicobacter pylori clinical isolates suggests resistance to metronidazole can occur without the loss of functional rdxA.
abstract: Resistance to metronidazole (MTZ) in Helicobacter pylori is associated with mutations in rdxA, encoding an oxygen-insensitive NADPH nitroreductase, and mutations in frxA, encoding a NAD(P)H-flavin oxidoreductase. Despite this association, the strict correlation of MTZ resistance with mutations in rdxA or frxA is still controversial. In this study, rdxA allelic replacement was used to distinguish resistance-associated nucleotide mutations from the natural genetic diversity of H. pylori. Replacement with truncated rdxA resulted in MTZ resistance, whereas replacement with missense-mutated rdxA from resistant clinical isolates failed to yield MTZ resistance. Thus, although truncation of rdxA confers MTZ resistance in G27 H. pylori, MTZ resistance found in other clinical isolates is not due to the identified amino-acid substitutions. Three of our MTZ-resistant clinical isolates expressed functional rdxA and two of these also encoded full-length frxA. Therefore, MTZ resistance can arise in H. pylori possessing functional rdxA, suggesting that other factors are involved in MTZ resistance.
authors.affiliation: Department of Oral Biology, Oral Science Research Center, BK21 Project, Yonsei University College of Dentistry, Seoul, Republic of Korea.
authors.forename: So Yeong
authors.initials: SY
authors.lastname: Kim
authors.forename: Young Min
authors.initials: YM
authors.lastname: Joo
authors.forename: Hak Sung
authors.initials: HS
authors.lastname: Lee
authors.forename: In-Sik
authors.initials: IS
authors.lastname: Chung
authors.forename: Yun-Jung
authors.initials: YJ
authors.lastname: Yoo
authors.forename: D Scott
authors.initials: DS
authors.lastname: Merrell
authors.forename: Jeong-Heon
authors.initials: JH
authors.lastname: Cha
mesh_terms: D000483:Alleles; D001426:Bacterial Proteins / Q000235:genetics*; D024881:Drug Resistance, Bacterial / Q000235:genetics*; D016480:Helicobacter pylori / Q000187:drug effects* / Q000235:genetics*; D008795:Metronidazole / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D009601:Nitroreductases / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014169:Transformation, Bacterial / Q000187:drug effects / Q000235:genetics
chemical_list: D001426:Bacterial Proteins; D008795:Metronidazole; D009601:Nitroreductases; C476646:RdxA protein, Helicobacter pylori