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Penicillin-binding proteins in beta-lactam-resistant laboratory mutants of Streptococcus pneumoniae
1Max-Planck Institut für molekulare Genetik, Berlin, FRG.
Abstract:
The increasing number of penicillin-resistant clinical strains of Streptococcus pneumoniae has raised questions about the mechanism involved. We have isolated a large number of independent, spontaneous laboratory mutants with increasing resistance against either piperacillin or cefotaxime. Both classes of mutants showed a different pathway of penicillin-binding protein (PBP) alterations, and within each group of mutants the individual PBPs appeared to have changed at different resistance levels and in different sequences. The mutations led to decreased beta-lactam affinity and possibly to a reduction in the amount of protein present in the cell, but differences in apparent molecular weight, like those reported in low- and high-level resistant pathogenic strains, were not found. Some mutants showed a high degree of cross-resistance to a variety of penicillins and cephalosporins independently of the acquired PBP alterations, indicating that different genotypes can be responsible for the same phenotypic expression of resistance.
Insights
Penicillin-resistant Streptococcus pneumoniae strains show varied resistance mechanisms. Laboratory mutants revealed distinct penicillin-binding protein (PBP) alterations and cross-resistance patterns, suggesting diverse genetic pathways to resistance.
Area of Science:
- Microbiology
- Molecular Biology
- Antimicrobial Resistance
Background:
- Increasing penicillin resistance in Streptococcus pneumoniae poses a significant public health concern.
- Understanding the molecular mechanisms underlying this resistance is crucial for developing effective treatments.
Purpose of the Study:
- To investigate the mechanisms of penicillin and cefotaxime resistance in Streptococcus pneumoniae.
- To characterize the alterations in penicillin-binding proteins (PBPs) associated with acquired resistance.
Main Methods:
- Isolation and characterization of spontaneous laboratory mutants of Streptococcus pneumoniae with increasing resistance to piperacillin or cefotaxime.
- Analysis of penicillin-binding protein (PBP) alterations in resistant mutants.
- Assessment of cross-resistance patterns to various penicillins and cephalosporins.
Main Results:
- Mutants exhibited distinct PBP alteration pathways for piperacillin and cefotaxime resistance.
- PBP changes occurred at different resistance levels and sequences within mutant groups.
- Mutations decreased beta-lactam affinity and potentially protein levels, but not apparent molecular weight.
- Some mutants displayed cross-resistance independent of PBP alterations, indicating diverse resistance genotypes.
Conclusions:
- Multiple genetic pathways contribute to beta-lactam resistance in Streptococcus pneumoniae.
- Penicillin-binding protein alterations are a key mechanism, but not the sole determinant of resistance.
- The study highlights the complexity of antimicrobial resistance and the potential for different genetic underpinnings of similar resistance phenotypes.