Penicillin-binding protein 2 and 4 (PBP2 and PBP4) (PBP2/4)

Penicillin-binding proteins (PBPs) are essential bacterial enzymes that catalyze the final steps of peptidoglycan synthesis, which is the primary structural component of the bacterial cell wall. PBP2 and PBP4 are specific members of this family that serve as critical high-affinity targets for several classes of beta-lactam antibiotics, most notably carbapenems such as imipenem and meropenem. In Gram-negative bacteria like Klebsiella pneumoniae and Escherichia coli, PBP2 is primarily responsible for maintaining the rod-like cell shape, while PBP4 is involved in peptidoglycan remodeling and maturation. The simultaneous high-affinity inhibition of these proteins by carbapenems leads to rapid bacterial killing, often characterized by the formation of spherical cells (spheroplasts) followed by lysis. In Staphylococcus aureus, PBP2 and PBP4 are vital for cell wall integrity and are considered the high-affinity native targets that are bypassed by the low-affinity PBP2a in methicillin-resistant strains (MRSA). Consequently, PBP2 and PBP4 are central to the mechanism of action of many broad-spectrum antibiotics and are key focal points in the study of bacterial resistance and the development of new therapeutic agents.

Other names

PBP2PBP4Penicillin-binding protein 2Penicillin-binding protein 4High-affinity PBPsNative PBPs 2 and 4

Inhibition of peptidoglycan transpeptidation and carboxypeptidation, leading to cell wall weakening, morphological changes (such as sphere formation), and eventual bacterial cell lysis and death.