Fig. 2. Mechanisms of Staphylococcus aureus resistance to penicillin (1), methicillin (3), and vancomycin (4). (A) Penicillin is inactivated by bacterial β-lactamases that hydrolyze the β-lactam ring, which forms an inactive penicilloic acid. (B) Resistance to methicillin, a modified-penicillin scaffold featuring a larger aryl side chain that is resistant to β-lactamase action, is driven by the expression of the alternative transpeptidase, PBP2a, which has a lower affinity for methicillin. Resistance to vancomycin results from modification of the terminal dipeptide of cell wall peptidoglycan chains, which reduces the affinity of the dipeptide for vancomycin.
