Penicillin-binding protein 1b, Penicillin-binding protein 1c, Penicillin-binding protein 2, and Penicillin-binding protein 3 (Pseudomonas aeruginosa) (PBP1b, PBP1c, PBP2, PBP3)

Penicillin-binding proteins (PBPs) are essential enzymes in Pseudomonas aeruginosa responsible for the final stages of peptidoglycan biosynthesis, which forms the bacterial cell wall (UniProt: P18502, P18503, P18504). Specifically, PBP1b and PBP1c are high-molecular-weight PBPs involved in cell wall elongation and maintenance. PBP2 (encoded by pbpA) and PBP3 (encoded by ftsI) are critical for maintaining cell shape and facilitating cell division or septation, respectively (PubMed: 16428818). These proteins are the primary targets for beta-lactam antibiotics, which act as pseudosubstrates that covalently bind to the active site serine residue, irreversibly inhibiting transpeptidase activity (StatPearls: NBK545275). In P. aeruginosa, PBP3 is a particularly vital target for many cephalosporins like ceftazidime and monobactams like aztreonam, whereas carbapenems often show high affinity for PBP2 (PubMed: 25941213). Inhibition of these proteins leads to the formation of filamentous cells or spheroplasts, ultimately resulting in bacterial cell lysis and death. Resistance mechanisms, such as mutations in the ftsI gene or the production of beta-lactamases, pose significant challenges in treating P. aeruginosa infections (PubMed: 30249623). Understanding the specific binding profiles of different antibiotics to these PBPs is crucial for developing effective treatments against multi-drug resistant strains.

Other names

PBPsMrcBPbpCPbpAFtsIPeptidoglycan glycosyltransferaseD-alanyl-D-alanine carboxypeptidasePenicillin-binding proteins 1b/1c/2/3

Inhibition of peptidoglycan transpeptidation by covalent binding to the active-site serine of penicillin-binding proteins, leading to cell wall degradation and bacterial lysis (PubMed: 25941213).