Correlation Between the Binding of β-Lactam Antibiotics to Staphylococcus aureus and Their Physical-Chemical Properties

Abstract

The rate of 14 C-benzylpenicillin (penicillin G) binding to Staphylococcus aureus Oxford cells increased with increasing hydrogen ion concentration. The extent of inhibition of 14 C-penicillin G binding caused by a competing 12 C-β-lactam antibiotic is a function of hydrogen ion concentration and can be correlated both with net charge of a competing 12 C-molecule and net charge of the S. aureus cell at a given p H. The ability of a β-lactam antibiotic to compete for 14 C-penicillin G-binding sites can generally be correlated with its hydrophobic nature. It is proposed that, although semisynthetic cephalosporins are chemically less reactive than penicillins, they are superior to benzylpenicillin in their ability to permeate the outer surface of the Staphylococcus cell wall and irreversibly bind to reactive sites.

Outer-Membrane Penetration Barriers as Components of Intrinsic Resistance to Beta-Lactam and Other Antibiotics in Escherichia coli K-12

“…The affinities of benzylpenicillin, ampicillin, cephalothin, and cephaloridine for the lysis-promoting target site(s) of Y10 are largely compatible with findings based on competitive binding 188 SCUDAMORE, BEVERIDGE, AND GOLDNER of beta-lactams to the isolated penicillin-binding protein 1 of E. coli (32). The low binding affinity of cloxacillin and cephalosporin C has been noted in other studies by using whole cells (24,26) and membrane preparations (3). Clearly, the poor antimicrobial activity of cloxacilhin is due both to poor penetration and low affinity.…”