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Alterations in penicillin-binding protein 1A confer resistance to beta-lactam antibiotics in Helicobacter pylori

M M Gerrits1, D Schuijffel, A A van Zwet

  • 1Department of Gastroenterology and Hepatology, Erasmus University Medical Center, Rotterdam, The Netherlands.

Antimicrobial Agents and Chemotherapy
|June 19, 2002
PubMed

Insights

A single amino acid change in penicillin-binding protein 1A (PBP1A) confers amoxicillin resistance in Helicobacter pylori. This discovery explains the mechanism behind the first stable amoxicillin-resistant H. pylori strain, aiding future eradication strategies.

Area of Science:

  • Microbiology
  • Molecular Biology
  • Drug Resistance

Background:

  • Amoxicillin is crucial for Helicobacter pylori eradication therapies.
  • The first stable amoxicillin-resistant clinical H. pylori isolate (Hardenberg strain) was previously identified.
  • The genetic basis for amoxicillin resistance in this strain remained unknown.

Purpose of the Study:

  • To elucidate the molecular mechanism of amoxicillin resistance in the Hardenberg strain of H. pylori.
  • To identify the specific genetic alterations responsible for beta-lactam resistance.

Main Methods:

  • Genetic analysis of the pbp1A gene in amoxicillin-sensitive and resistant H. pylori strains.
  • Gene replacement experiments to assess the functional impact of pbp1A mutations.
  • Determination of minimum inhibitory concentrations (MICs) for amoxicillin.

Main Results:

  • A single amino acid substitution (Ser414Arg) in HP0597, a penicillin-binding protein 1A (PBP1A) homolog, was identified as the cause of resistance.
  • Replacing the wild-type pbp1A gene with the Hardenberg strain's gene in a sensitive strain increased amoxicillin MIC 100-fold.
  • This specific substitution in PBP1A was sufficient to confer amoxicillin resistance comparable to the original Hardenberg strain.

Conclusions:

  • The beta-lactam resistance in the Hardenberg H. pylori strain is primarily due to a specific amino acid substitution in PBP1A.
  • This finding provides a molecular explanation for amoxicillin resistance in H. pylori.
  • Understanding this mechanism is vital for developing effective H. pylori treatment strategies.

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