Pseudomonas aeruginosa penicillin-binding protein 2 (PBP2)

Pseudomonas aeruginosa penicillin-binding protein 2 (PBP2) is a high-molecular-weight class B transpeptidase encoded by the mrdA gene (UniProt, 2024). It plays a vital role in the biosynthesis of the bacterial cell wall by catalyzing the cross-linking of peptidoglycan chains, which is essential for maintaining the structural integrity and rod-like shape of the organism (PubMed, 2021). PBP2 is a significant therapeutic target for beta-lactam antibiotics, particularly carbapenems like imipenem, which show a high binding affinity for this specific protein in P. aeruginosa (NCBI, 2023). When PBP2 is inhibited, the bacteria fail to maintain their shape and transform into spherical cells known as spheroplasts, which eventually undergo osmotic lysis and death (Journal of Bacteriology, 2019). This target is clinically relevant in treating severe infections caused by P. aeruginosa, including those found in cystic fibrosis patients and hospital-acquired pneumonia (StatPearls, 2023). However, the efficacy of drugs targeting PBP2 is often challenged by the emergence of resistance mechanisms, such as target site mutations in the mrdA gene or the upregulation of multidrug efflux pumps (Frontiers in Microbiology, 2022). Additionally, some beta-lactams targeting PBP2 can induce the expression of chromosomal beta-lactamases like AmpC, further complicating treatment strategies (Antimicrobial Agents and Chemotherapy, 2020).

Other names

Penicillin-binding protein 2PBP-2Peptidoglycan D-amino acid transpeptidasemrdA

Inhibition of the transpeptidase activity of penicillin-binding protein 2, which prevents the cross-linking of peptidoglycan chains in the bacterial cell wall, leading to the formation of spherical cells and subsequent osmotic lysis.