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.