SATURATION OF PENICILLIN-BINDING PROTEIN-1 BY BETA-LACTAM ANTIBIOTICSIN GROWING CELLS OF BACILLUS-LICHENIFORMIS

With the help of a new highly sensitive method allowing the quantifica tion of free penicillin-binding proteins (PBPs) and of an integrated m athematical model, the progressive saturation of PBP1 by various beta- lactam antibiotics in growing cells of Bacillus licheniformis was stud ied. Although the results confirmed PBP1 as a major lethal target for these compounds, they also underlined several weaknesses in our presen t understanding of this phenomenon. In growing cells, but not in resti ng cells, the penicillin target(s) appeared to be somewhat protected f rom the action of the inactivators. In vitro experiments indicated tha t amino acids, peptides and depsipeptides mimicking the peptide moiety of the nascent peptidoglycan significantly interfered with the acylat ion of PBP1 by the antibiotics. In addition, the level of PBP1 saturat ion at antibiotic concentrations corresponding to the minimum inhibito ry concentrations was not constant, suggesting that additional, presen tly undiscovered, factors might be necessary to account for the experi mental observations.