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Penicillin-binding protein 2x of Streptococcus pneumoniae: three new mutational pathways for remodelling an essential

Patrick Maurer1, Barbara Koch, Ilka Zerfass

  • 1Department of Microbiology, University of Kaiserslautern, Paul-Ehrlich Strasse 23, D-67663 Kaiserslautern, Germany.

Journal of Molecular Biology
|February 1, 2008
PubMed

Insights

Mutations in Streptococcus pneumoniae penicillin-binding protein 2x (PBP2x) reduce beta-lactam affinity, driving antibiotic resistance. Different mutation patterns in PBP2x influence cefotaxime and benzylpenicillin resistance, impacting treatment strategies.

Area of Science:

  • Microbiology
  • Molecular Biology
  • Pharmacology

Background:

  • Penicillin-binding protein 2x (PBP2x) mutations in Streptococcus pneumoniae are key to beta-lactam antibiotic resistance.
  • Understanding these mutations is crucial for developing effective treatments against resistant strains.

Purpose of the Study:

  • To analyze the in vitro and in vivo properties of PBP2x variants from cefotaxime-resistant Streptococcus pneumoniae.
  • To categorize PBP2x mutations based on their structural positions and impact on beta-lactam resistance.

Main Methods:

  • Analysis of PBP2x variants from laboratory mutants and a clinical isolate.
  • Characterization of mutation patterns and their proximity to the active site.
  • Measurement of acylation efficiencies for beta-lactam antibiotics.

Main Results:

  • Three distinct groups of PBP2x mutations were identified, categorized by their structural location.
  • Group I mutations showed significantly reduced acylation efficiency for cefotaxime.
  • Group II mutations, including L403F, drastically reduced efficiency for both cefotaxime and benzylpenicillin.
  • Group III mutations (Q552E, S389L) also reduced acylation efficiency for both antibiotics.

Conclusions:

  • Specific PBP2x mutation patterns dictate the level and type of beta-lactam resistance in Streptococcus pneumoniae.
  • Mutations near the active site are critical for conferring resistance, with some mediating resistance alone.
  • Further research into these mutation pathways can inform strategies against antibiotic resistance.

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