Penicillin-binding protein 1A, 2B, and 2X alterations in Canadian isolates of penicillin-resistant Streptococcus

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Kimberly A Nichol1, George G Zhanel, Daryl J Hoban

  • 1Department of Medical Microbiology, Faculty of Medicine, University of Manitoba, Canada. knichol@hsc.mb.ca

Antimicrobial Agents and Chemotherapy
|September 18, 2002
PubMed

Insights

Penicillin resistance in Streptococcus pneumoniae is linked to specific alterations in penicillin-binding protein (PBP) genes. These changes in PBP 1A, PBP 2B, and PBP 2X are crucial for understanding antibiotic resistance mechanisms.

Area of Science:

  • Microbiology
  • Molecular Biology
  • Antimicrobial Resistance

Background:

  • Streptococcus pneumoniae is a leading cause of bacterial infections worldwide.
  • Penicillin resistance in S. pneumoniae is a growing public health concern.
  • Penicillin-binding proteins (PBPs) are the primary targets of beta-lactam antibiotics like penicillin.

Purpose of the Study:

  • To investigate the specific alterations in penicillin-binding protein (PBP) genes (pbp1a, pbp2b, and pbp2x) in Canadian isolates of Streptococcus pneumoniae.
  • To correlate these genetic alterations with penicillin non-susceptibility.
  • To identify common substitution patterns associated with high-level penicillin resistance.

Main Methods:

  • Genomic DNA extraction from 15 Canadian S. pneumoniae isolates.
  • Sequence analysis of the penicillin-binding domains of pbp1a, pbp2b, and pbp2x genes.
  • Determination of penicillin Minimum Inhibitory Concentrations (MICs).
  • Correlation of PBP gene alterations with observed penicillin MIC values.

Main Results:

  • All penicillin-nonsusceptible S. pneumoniae isolates exhibited diverse PBP 2X substitutions.
  • A consistent Thr445-Ala change was observed in PBP 2B following the SSN motif in resistant isolates.
  • PBP 1A alterations near the STMK and SRN motifs were present only in isolates with penicillin MICs ≥ 0.5 μg/mL.
  • Identical PBP 1A, PBP 2B, and PBP 2X substitution patterns were found in all isolates with penicillin MICs ≥ 1 μg/mL.

Conclusions:

  • Specific amino acid substitutions in PBP 1A, PBP 2B, and PBP 2X are strongly associated with penicillin resistance in S. pneumoniae.
  • The identified PBP alterations provide molecular markers for predicting and understanding penicillin resistance.
  • These findings contribute to the ongoing surveillance and management of antibiotic-resistant S. pneumoniae infections.

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