Gut Liver.  2013 Nov;7(6):655-660.

Substitutions in Penicillin-Binding Protein 1 in Amoxicillin-Resistant Helicobacter pylori Strains Isolated from Korean Patients

• Kim BJ
• Kim JG

Abstract

BACKGROUND/AIMS
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 microg/mL.
RESULTS
Nine of 150 H. pylori strains showed amoxicillin resistance (6%). The MIC values of the resistant strains ranged from 1 to 4 microg/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.

Keyword

Helicobacter pylori; Amoxicillin resistance; Penicillin-binding proteins; Amino acid substitution

MeSH Terms

Adult
Amino Acid Sequence
*Amino Acid Substitution
Amoxicillin/*pharmacology
Anti-Bacterial Agents/*pharmacology
Female
Helicobacter Infections/drug therapy
Helicobacter pylori/*chemistry/*drug effects/genetics
Humans
Male
Microbial Sensitivity Tests
Middle Aged
*Penicillin Resistance/genetics
Penicillin-Binding Proteins/*chemistry/genetics
Republic of Korea
Sequence Analysis, Protein
Transformation, Genetic
Anti-Bacterial Agents
Amoxicillin
Penicillin-Binding Proteins