title: Substitutions in penicillin-binding protein 1 in amoxicillin-resistant Helicobacter pylori strains isolated from Korean patients.
abstract: OBJECTIVE
  A worldwide increase in amoxicillin resistance in Helicobacter pylori is having an adverse effect on eradication therapy. In this study, we investigated the mechanism of the amoxicillin resistance of H. pylori in terms of amino acid substitutions in penicillin-binding protein 1 (PBP1).
  
  
  METHODS
  In total, 150 H. pylori strains were isolated from 144 patients with chronic gastritis, peptic ulcers, or stomach cancer. The minimum inhibitory concentrations (MICs) of the strains were determined with a serial 2-fold agar dilution method. The resistance breakpoint for amoxicillin was defined as >0.5 µg/mL.
  
  
  RESULTS
  Nine of 150 H. pylori strains showed amoxicillin resistance (6%). The MIC values of the resistant strains ranged from 1 to 4 µg/mL. A PBP1 sequence analysis of the resistant strains revealed multiple amino acid substitutions: Val16→Ile, Val45→Ile, Ser414→Arg, Asn562→Tyr, Thr593→Ala, Gly595→Ser, and Ala599→Thr. The natural transformation of these mutated genes into amoxicillin-sensitive strains was performed in two separate pbp1 gene segments. A moderate increase in the amoxicillin MIC was observed in the segment that contained the penicillin-binding motif of the C-terminal portion, the transpeptidase domain.
  
  
  CONCLUSIONS
  pbp1 mutation affects the amoxicillin resistance of H. pylori through the transfer of the penicillin-binding motif.
authors: Department of Internal Medicine, Chung-Ang University Hospital, Chung-Ang University College of Medicine, Seoul, Korea.
authors: Beom Jin
authors: BJ
authors: Kim
authors: Jae G
authors: JG
authors: Kim
mesh_terms: D000328:Adult; D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D000658:Amoxicillin / Q000494:pharmacology*; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D005260:Female; D016481:Helicobacter Infections / Q000188:drug therapy; D016480:Helicobacter pylori / Q000737:chemistry* / Q000187:drug effects* / Q000235:genetics; D006801:Humans; D008297:Male; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D010403:Penicillin Resistance / Q000235:genetics; D046915:Penicillin-Binding Proteins / Q000737:chemistry* / Q000235:genetics; D056910:Republic of Korea; D020539:Sequence Analysis, Protein; D014170:Transformation, Genetic
chemical_list: D000900:Anti-Bacterial Agents; D046915:Penicillin-Binding Proteins; D000658:Amoxicillin
keywords: Amino acid substitution; Amoxicillin resistance; Helicobacter pylori; Penicillin-binding proteins