Saturation of penicillin-binding protein 1 by beta-lactam antibiotics in growing cells of Bacillus licheniformis.
With the help of a new highly sensitive method allowing the quantification of free penicillin-binding proteins (PBPs) and of an integrated mathematical model, the progressive saturation of PBP1 by various beta-lactam antibiotics in growing cells of Bacillus licheniformis was studied. Although the results confirmed PBP1 as a major lethal target for these compounds, they also underlined several weaknesses in our present understanding of this phenomenon. In growing cells, but not in resting cells, the penicillin target(s) appeared to be somewhat protected from the action of the inactivators. In vitro experiments indicated that amino acids, peptides and depsipeptides mimicking the peptide moiety of the nascent peptidoglycan significantly interfered with the acylation of PBP1 by the antibiotics. In addition, the level of PBP1 saturation at antibiotic concentrations corresponding to the minimum inhibitory concentrations was not constant, suggesting that additional, presently undiscovered, factors might be necessary to account for the experimental observations.
Lepage
S
S
Laboratoire d'Enzymologie et Centre d'Ingénierie des Protéines, Université de Liège, Sart Tilman, Belgium.
Lakaye
B
B
Galleni
M
M
Thamm
I
I
Crine
M
M
Groslambert
S
S
Frère
J M
JM
D000215:Acylation; D000596:Amino Acids / Q000378:metabolism; D000900:Anti-Bacterial Agents / Q000378:metabolism* / Q000494:pharmacology; D001407:Bacillus / Q000254:growth & development / Q000378:metabolism*; D001426:Bacterial Proteins; D002352:Carrier Proteins / Q000378:metabolism*; D002507:Cephaloglycin / Q000378:metabolism; D002511:Cephalosporins / Q000378:metabolism; D003023:Cloxacillin / Q000378:metabolism; D004952:Esters / Q000378:metabolism; D006602:Hexosyltransferases; D007700:Kinetics; D008826:Microbial Sensitivity Tests; D008958:Models, Molecular; D002267:Muramoylpentapeptide Carboxypeptidase / Q000378:metabolism*; D046915:Penicillin-Binding Proteins; D010406:Penicillins / Q000378:metabolism*; D010455:Peptides / Q000378:metabolism; D010458:Peptidyl Transferases; D013379:Substrate Specificity; D013438:Sulfhydryl Compounds / Q000378:metabolism
D000596:Amino Acids; D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D002352:Carrier Proteins; D002511:Cephalosporins; D004952:Esters; D046915:Penicillin-Binding Proteins; D010406:Penicillins; D010455:Peptides; D013438:Sulfhydryl Compounds; C025163:cephalosporin C; D010458:Peptidyl Transferases; D006602:Hexosyltransferases; D002267:Muramoylpentapeptide Carboxypeptidase; D002507:Cephaloglycin; D003023:Cloxacillin