KINETICS OF PENICILLIN-BINDING TO PENICILLIN-BINDING PROTEINS OF STAPHYLOCOCCUS-AUREUS

Reduced affinity of penicillin-binding proteins (PBPs) for binding pen icillin has been proposed as a mechanism of beta-lactam antibiotic res istance in staphylococci. Penicillin binding by PBPs of three penicill in-susceptible and two penicillin-resistant strains of Staphylococcus aureus was studied in kinetic assays to determine rate constants, drug concentrations at which PBPs were bound and the relationship between concentrations that bound PBPs and concentrations that inhibited bacte rial growth. PBPs 1 and 2 of the resistant strains exhibited slower ac ylation and more rapid deacylation than susceptible strains. In contra st PBP 4, a naturally low-affinity PBP, was modified such that it exhi bited a lower rate of deacylation. The concentrations of penicillin at which modified PBPs were bound correlated with concentrations that in hibited growth of the resistant strains. Acquisition of penicillin res istance in these strains of S. aureus results, at least in part, from structural modifications affecting binding of multiple PBPs and appear s to include recruitment of a non-essential PBP, PBP 4.