title: Characterisation of the genes encoding resistance to metronidazole (rdxA and frxA) and clarithromycin (the 23S-rRNA genes) in South African isolates of Helicobacter pylori.
abstract: Helicobacter pylori has been incriminated in human diseases, such as peptic ulcer, gastritis and gastric malignancy. Although modern triple-drug regimens are usually highly effective in the treatment of H. pylori infection, the emergence of resistance to two of the most used antibiotics, metronidazole (Mtz) and clarithromycin (Cla), is a serious and increasing problem. Truncations in the rdxA and frxA genes of H. pylori are thought to be associated with Mtz resistance whereas mutations in the pathogen's 23S-ribosomal-RNA (23S-rRNA) genes are associated with Cla resistance. In a recent study, PCR and sequence analysis of the rdxA, frxA and 23S-rRNA genes were used to explore the genetic basis of resistance to Mtz and Cla in H. pylori. When 200 isolates of H. pylori from the Eastern Cape province of South Africa were tested for antibiotic susceptibility, almost all (95·5%) were found resistant to Mtz and 20·0% were found resistant to Cla. Only the Mtz-resistant isolates showed rdxA and frxA truncation. Two point mutations were detected in the 23S-rRNA genes of the Cla-resistant isolates. Many significant changes (resulting in 13 amino-acid substitutions in nine loci and truncated proteins in 14 loci) were observed in the rdxA genes of the Mtz-resistant isolates, and it appears that, compared with the rarer changes detected in frxA, such mutations may contribute more significantly to the high prevalence of Mtz resistance. To guide empiric treatment, the genotypes and antibiotic susceptibility of H. pylori in the Eastern Cape province of South Africa need to be monitored regularly.
authors.affiliation: Microbial Pathogenicity and Molecular Epidemiology Research Group, Department ofBiochemistry and Microbiology, Faculty of Science and Agriculture, University of Fort Hare, Alice 5700, South Africa.
authors.forename: N F
authors.initials: NF
authors.lastname: Tanih
authors.forename: L M
authors.initials: LM
authors.lastname: Ndip
authors.forename: R N
authors.initials: RN
authors.lastname: Ndip
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D017291:Clarithromycin / Q000494:pharmacology*; D004269:DNA, Bacterial / Q000302:isolation & purification; D024881:Drug Resistance, Bacterial / Q000235:genetics*; D038181:FMN Reductase / Q000235:genetics; D005260:Female; D005798:Genes, Bacterial; D016481:Helicobacter Infections / Q000188:drug therapy / Q000382:microbiology*; D016480:Helicobacter pylori / Q000187:drug effects / Q000235:genetics*; D006801:Humans; D008297:Male; D008795:Metronidazole / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests / Q000379:methods; D008875:Middle Aged; D009601:Nitroreductases / Q000235:genetics; D016133:Polymerase Chain Reaction / Q000379:methods; D012338:RNA, Ribosomal, 23S / Q000235:genetics; D055815:Young Adult
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D004269:DNA, Bacterial; D012338:RNA, Ribosomal, 23S; D008795:Metronidazole; D038181:FMN Reductase; D009601:Nitroreductases; C476646:RdxA protein, Helicobacter pylori; D017291:Clarithromycin