Penicillin-binding protein 2 (PBP2) (PBP2)

Penicillin-binding protein 2 (PBP2) is a critical enzyme located in the periplasmic space of Gram-negative bacteria, particularly within the Enterobacteriaceae family [UniProt, 2024]. It functions primarily as a transpeptidase, catalyzing the cross-linking of peptidoglycan polymers, which is a vital step in the biosynthesis and structural maintenance of the bacterial cell wall [StatPearls, 2023]. PBP2 is uniquely responsible for maintaining the rod-like shape of these bacteria; its inhibition typically results in the formation of spherical cells (spheroplasts) and eventual osmotic lysis [PubMed, 2018]. Related PBPs in Enterobacteriaceae, such as PBP1a, PBP1b, and PBP3, also play critical roles in cell wall elongation and septation, often serving as co-targets for broad-spectrum beta-lactams [StatPearls, 2023]. PBP2 is the primary target of the narrow-spectrum penicillin mecillinam and is also targeted by various carbapenems and novel diazabicyclooctane (DBO) inhibitors like zidebactam [PubChem, 2024; PubMed, 2021]. Because PBPs are located on the outer face of the cytoplasmic membrane, they are accessible to drugs that can penetrate the outer membrane of Gram-negative pathogens [StatPearls, 2023]. Understanding the interplay between PBP2 and its related proteins is crucial for overcoming multi-drug resistance, as modifications in these targets or their expression levels can significantly reduce antibiotic efficacy [Journal of Antimicrobial Chemotherapy, 2020].

Other names

mrdAPeptidoglycan D-amino acid transpeptidasePBP-2Penicillin-binding protein 1a (PBP1a)Penicillin-binding protein 1b (PBP1b)Penicillin-binding protein 3 (PBP3)ftsI

Covalent inhibition of the transpeptidase domain of PBP2 and related penicillin-binding proteins, preventing the cross-linking of peptidoglycan strands, which leads to cell wall defects, spheroplast formation, and bacterial cell death [StatPearls, 2023; UniProt, 2024].