Persistent acylation of high-molecular-weight penicillin-binding proteins by penicillin induces the postantibiotic effect in Streptococcus pyogenes.
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.
Yan
S
S
Department of Microbiology, Molecular Biology and Biochemistry, University of Idaho, Moscow.
Bohach
G A
GA
Stevens
D L
DL
D000215:Acylation; D001426:Bacterial Proteins; D002352:Carrier Proteins / Q000096:biosynthesis / Q000302:isolation & purification / Q000378:metabolism*; D002462:Cell Membrane / Q000187:drug effects / Q000648:ultrastructure; D002981:Clindamycin / Q000494:pharmacology* / Q000633:toxicity; D006602:Hexosyltransferases; D007700:Kinetics; D008239:Lysine / Q000378:metabolism; D008565:Membrane Proteins / Q000187:drug effects / Q000302:isolation & purification / Q000378:metabolism; D008826:Microbial Sensitivity Tests; D008855:Microscopy, Electron, Scanning; D002267:Muramoylpentapeptide Carboxypeptidase / Q000096:biosynthesis / Q000302:isolation & purification / Q000378:metabolism*; D010400:Penicillin G / Q000494:pharmacology* / Q000633:toxicity; D046915:Penicillin-Binding Proteins; D010458:Peptidyl Transferases; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D013297:Streptococcus pyogenes / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D013997:Time Factors
D001426:Bacterial Proteins; D002352:Carrier Proteins; D008565:Membrane Proteins; D046915:Penicillin-Binding Proteins; D011500:Protein Synthesis Inhibitors; D002981:Clindamycin; D010458:Peptidyl Transferases; D006602:Hexosyltransferases; D002267:Muramoylpentapeptide Carboxypeptidase; D008239:Lysine; D010400:Penicillin G