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Persistent acylation of high-molecular-weight penicillin-binding proteins by penicillin induces the postantibiotic
S Yan1, G A Bohach, D L Stevens
1Department of Microbiology, Molecular Biology and Biochemistry, University of Idaho, Moscow.
Abstract:
Penicillin at 10X MIC induced a postantibiotic effect (PAE) of 2.1 h in Streptococcus pyogenes. Progressive increases in the densities of penicillin-binding proteins (PBPs) 1-3 of the bacterium were detected at 30, 60, and 90 min during the postantibiotic phase. The increase in colony-forming units during this phase paralleled the kinetics of incorporation of lysine into proteins, suggesting that growth was triggered by de novo synthesis of PBPs. The question was raised as to whether the progressive increases in densities of PBPs were due to the restoration of preexisting PBPs or to synthesis of new PBPs. With 10X MIC of clindamycin to inhibit PBP synthesis during the postantibiotic phase, the temporal increase in densities of PBPs 1-3 were totally inhibited. These results suggest that the PAE of penicillin in S. pyogenes is caused by irreversible binding of penicillin to PBPs 1-3 and represents the time necessary for synthesis of new PBPs required for normal growth.
Insights
Penicillin
Area of Science:
- Microbiology
- Pharmacology
- Molecular Biology
Background:
- Penicillin's postantibiotic effect (PAE) is crucial for understanding bacterial regrowth after antibiotic exposure.
- Penicillin-binding proteins (PBPs) are essential for bacterial cell wall synthesis and are primary targets for penicillin action.
Purpose of the Study:
- To investigate the mechanism underlying the postantibiotic effect of penicillin in Streptococcus pyogenes.
- To determine whether the increase in penicillin-binding proteins (PBPs) during the postantibiotic phase is due to restoration or de novo synthesis.
Main Methods:
- Streptococcus pyogenes cultures were exposed to penicillin at 10X MIC to induce PAE.
- Penicillin-binding protein (PBP) densities were quantified during the postantibiotic phase.
- Protein synthesis was inhibited using clindamycin to assess its role in PBP restoration.
Main Results:
- Penicillin induced a 2.1-hour PAE in Streptococcus pyogenes.
- Progressive increases in penicillin-binding proteins (PBPs) 1-3 were observed during the PAE, correlating with protein synthesis.
- Clindamycin treatment completely inhibited PBP increases, indicating de novo synthesis is required.
Conclusions:
- The postantibiotic effect of penicillin in Streptococcus pyogenes is attributed to the irreversible binding of penicillin to PBPs 1-3.
- Bacterial regrowth during PAE is dependent on the time required for the synthesis of new PBPs.
- This study elucidates the molecular mechanism behind penicillin's PAE, highlighting the importance of PBP synthesis for bacterial recovery.