Penicillin-binding protein of Pseudomonas aeruginosa (PBP) (PBP)

Penicillin-binding proteins (PBPs) are essential membrane-associated enzymes in Pseudomonas aeruginosa that catalyze the final steps of peptidoglycan biosynthesis, which is vital for maintaining bacterial structural integrity [UniProt: P11077]. These enzymes are classified into high-molecular-weight (HMW) PBPs, which possess transpeptidase and often transglycosylation activity, and low-molecular-weight (LMW) PBPs, which function primarily as carboxypeptidases or endopeptidases [PubMed: 19151196]. In P. aeruginosa, PBP3 (encoded by ftsI) is a particularly critical target for many anti-pseudomonal beta-lactams, including ceftazidime and aztreonam, as its inhibition leads to filamentation and cell death [PubMed: 21673134]. The interaction between these drugs and PBPs involves the formation of a stable acyl-enzyme complex that halts the cross-linking of the cell wall. Resistance to these agents often arises through PBP mutations that decrease drug affinity or through the overproduction of certain PBPs like PBP4, which can also trigger the induction of AmpC beta-lactamases [PubMed: 19151196]. Because PBPs are unique to bacteria and absent in human cells, they serve as highly effective therapeutic targets for treating severe infections. Understanding the diversity and function of PBPs is crucial for developing new strategies to combat multi-drug resistant P. aeruginosa infections.

Other names

DD-transpeptidaseDD-carboxypeptidaseMurein synthasePeptidoglycan synthaseFtsIDacBPonAPBP3PBP1aPBP1bPBP2PBP4

Beta-lactam antibiotics act as structural analogs of the D-alanyl-D-alanine terminus of peptidoglycan precursors, covalently binding to the active-site serine of PBPs to inhibit the transpeptidation reaction required for peptidoglycan cross-linking, which leads to cell wall instability and bacterial lysis [StatPearls: NBK545311].