Penicillin-binding proteins and bacterial resistance to β-lactams

Susceptibility to beta -lactam antibiotics reflects the combined effects of binding to targets (penicillin-binding proteins [PBPs]), stability to beta -lactamases, and, in gram-negative bacteria, outer-membrane permeability. Similarly, resistance reflects a change in any of the three components. The major enzymatic activities associated with PBPs are peptidoglycan transpeptidase, which is believed to be essential, and DD-carboxypeptidase, which is believed to be dispensable. To date, only PBPs with DD-carboxypeptidase activity have been examined in any great detail. Some PBPs, particularly those of low molecular weight, also have weak beta -lactamase activity which, although of no major physiological significance, may nevertheless interfere with PBP binding studies in intact bacteria. A given organism contains four to eight PBPs with molecular sizes of 35 to 120 kDa. Altered PBPs associated with beta -lactam resistance are more commonly found in gram-positive than in gram-negative bacteria.