Variation in penicillin-binding protein patterns of penicillin-resistant clinical isolates of pneumococci

Z Markiewicz1, A Tomasz

  • 1Laboratory of Microbiology, Rockefeller University, New York, New York 10021.

Insights

Penicillin-resistant Streptococcus pneumoniae strains often lose penicillin-binding protein 1A and PBP 2B. Diverse alterations in penicillin-binding proteins contribute to varying levels of penicillin resistance in pneumococcal isolates.

Area of Science:

  • Microbiology
  • Molecular Biology
  • Pharmacology

Background:

  • Penicillin resistance in Streptococcus pneumoniae is a growing public health concern.
  • Penicillin-binding proteins (PBPs) are the primary targets of penicillin antibiotics.
  • Understanding the molecular mechanisms of penicillin resistance is crucial for developing effective treatments.

Purpose of the Study:

  • To investigate the alterations in penicillin-binding protein (PBP) patterns associated with penicillin resistance in Streptococcus pneumoniae.
  • To correlate specific PBP changes with different levels of penicillin minimum inhibitory concentrations (MICs).

Main Methods:

  • Analysis of over 80 pneumococcal isolates with a wide range of penicillin resistance levels (MICs from 0.003 to 16 µg/ml).
  • Characterization of penicillin-binding protein (PBP) profiles using techniques like fluorography with radioactive penicillin.
  • Comparison of PBP patterns between susceptible and resistant strains.

Main Results:

  • Strains with low penicillin MICs (up to ~0.05 µg/ml) typically possessed five PBPs similar to susceptible strains.
  • Strains with higher penicillin MICs (≥0.1 µg/ml) commonly showed loss of PBP 1A and sometimes a new PBP (96-97 kDa).
  • In highly resistant strains (MICs ≥0.5 µg/ml), PBP 2B was undetectable. Diverse PBP profiles were observed among resistant strains with similar MICs.

Conclusions:

  • Alterations in penicillin-binding proteins, particularly PBP 1A and PBP 2B, are key determinants of penicillin resistance in Streptococcus pneumoniae.
  • Multiple distinct modifications in critical PBPs can lead to comparable levels of penicillin resistance.
  • Further research into PBP remodeling is warranted to understand pneumococcal resistance mechanisms.

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