Pbps

Penicillin-binding proteins (PBPs) are a family of enzymes in bacteria that catalyze essential steps in the synthesis and remodeling of peptidoglycan, the main structural component of the bacterial cell wall. They include transglycosylases that polymerize glycan strands and transpeptidases that cross-link peptide side chains, providing cell wall rigidity. PBPs are named for their susceptibility to covalent inactivation by beta-lactam antibiotics such as penicillin and related drugs.

PBPs are classified by size and function. High-molecular-mass PBPs (classes A and B) generally carry out glycosyltransferase and transpeptidase activities (class A) or primarily transpeptidation (class B). Low-molecular-mass PBPs usually act as DD-carboxypeptidases or endopeptidases, aiding cell wall remodeling. The specific set and roles of PBPs vary among bacterial species and can affect essentiality and drug response.

Mechanism and antibiotic interaction. PBPs catalyze the cross-linking of peptide side chains in peptidoglycan during cell wall synthesis. Beta-lactam antibiotics resemble the natural substrate’s terminal dipeptide and bind irreversibly to the active-site serine of PBPs, inhibiting their enzymatic activity and weakening the cell wall, which often leads to cell lysis in dividing bacteria. Resistance can arise from mutations that reduce PBP affinity for beta-lactams or from acquisition of alternative PBPs with low drug affinity (for example, PBP2a in MRSA).

Clinical relevance. PBPs are primary targets of beta-lactam antibiotics and play a central role in determining bacterial susceptibility and resistance profiles. Laboratory and clinical studies frequently examine PBP profiles to understand drug responses and to guide antibiotic selection.