Penicillin-binding protein 2 (Pseudomonas aeruginosa) (PBP2)

Penicillin-binding protein 2 (PBP2) is an essential enzyme in the Gram-negative bacterium Pseudomonas aeruginosa, where it functions as a transpeptidase involved in the synthesis and cross-linking of the peptidoglycan layer (UniProt: P0A244). Encoded by the mrdA gene, PBP2 is a Class B high-molecular-weight PBP that is critical for maintaining the structural integrity and rod-shaped morphology of the cell (PubMed: 29066486). In P. aeruginosa, PBP2 is a primary target for carbapenem antibiotics, such as imipenem and meropenem, which bind to its active site to prevent cell wall formation (PubMed: 10681328). The specific strain SC8329 is a clinical isolate frequently used in the development of novel antibiotics like zidebactam, a non-beta-lactam inhibitor that specifically targets PBP2 to enhance the activity of co-administered drugs (PubMed: 28242668). Inhibition of PBP2 typically results in the formation of spherical cells that are susceptible to osmotic lysis, making it a key target for treating severe infections caused by multi-drug resistant P. aeruginosa (PubMed: 30247485).

Other names

mrdAPeptidoglycan transpeptidase PBP2PBP-2D-alanyl-D-alanine transpeptidase PBP2Penicillin-binding protein 2

Inhibition of the transpeptidase activity by covalent binding to the active-site serine residue, preventing the cross-linking of peptidoglycan chains and leading to cell wall instability.