title: Clarithromycin Resistance Mutations in Helicobacter pylori in Association with Virulence Factors and Antibiotic Susceptibility of the Strains.
abstract: Antibiotic resistance is the major cause for Helicobacter pylori eradication failure. H. pylori clarithromycin resistance mutations were evaluated in 84 (82 phenotypically clarithromycin resistant and 2 intermediately susceptible) strains by allele-specific PCR and 3'-mismatched PCR. Many (57.1%) of these strains were metronidazole resistant. Prevalence of cagA(+), cagE(+), vacA s1a, m1, i1, and i2 strains was 76.2%, 58.0%, 82.1%, 35.7%, 50.0%, and 50.0%, respectively. A2143G, A2142G, A2142C, and A2143G+A2142G mutation rates were 64.3%, 23.8%, 1.2%, and 10.7%, respectively. Strains harboring the A2142G mutation showed 5.3-fold higher clarithromycin MIC50 than those harboring the A2143G mutation. The A2143G mutation alone was 1.7-fold more common in vacA i2 strains compared with vacA i1 strains, while the A2142G mutation alone was 3-fold more frequent in vacA i1 strains than vacA i2 strains and 3.1-fold more common in metronidazole-susceptible compared with metronidazole-resistant strains. Briefly, clarithromycin resistance mutations were significantly linked to vacA i allele and metronidazole susceptibility. This is the first report about associations between the A2143G mutation and less virulent vacA i2 strains, and between the A2142G mutation and more virulent vacA i1 strains. As the 2143G mutation often predicts eradication failure by clarithromycin-based regimens, the results may be linked to the better eradication of more virulent strains compared with the less virulent strains.
authors.affiliation: Department of Medical Microbiology, Medical University of Sofia , Sofia, Bulgaria .
authors.forename: Lyudmila
authors.initials: L
authors.lastname: Boyanova
authors.affiliation: Department of Medical Microbiology, Medical University of Sofia , Sofia, Bulgaria .
authors.forename: Rumyana
authors.initials: R
authors.lastname: Markovska
authors.affiliation: Department of Medical Microbiology, Medical University of Sofia , Sofia, Bulgaria .
authors.forename: Daniel
authors.initials: D
authors.lastname: Yordanov
authors.affiliation: Department of Medical Microbiology, Medical University of Sofia , Sofia, Bulgaria .
authors.forename: Galina
authors.initials: G
authors.lastname: Gergova
authors.affiliation: Department of Medical Microbiology, Medical University of Sofia , Sofia, Bulgaria .
authors.forename: Ivan
authors.initials: I
authors.lastname: Mitov
mesh_terms: D000328:Adult; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001426:Bacterial Proteins / Q000235:genetics; D002648:Child; D017291:Clarithromycin / Q000494:pharmacology*; D004269:DNA, Bacterial / Q000235:genetics; D024881:Drug Resistance, Bacterial / Q000187:drug effects* / Q000235:genetics*; D005260:Female; D016481:Helicobacter Infections / Q000188:drug therapy / Q000382:microbiology; D016480:Helicobacter pylori / Q000187:drug effects* / Q000235:genetics*; D006801:Humans; D008297:Male; D008795:Metronidazole; D008826:Microbial Sensitivity Tests / Q000379:methods; D009154:Mutation / Q000235:genetics*; D037521:Virulence Factors / Q000235:genetics*
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D004269:DNA, Bacterial; D037521:Virulence Factors; D008795:Metronidazole; D017291:Clarithromycin