Pseudomonas aeruginosa penicillin-binding protein 3 (PBP3) (PBP3)

Penicillin-binding protein 3 (PBP3) is an essential enzyme in Pseudomonas aeruginosa, encoded by the ftsI gene, that plays a pivotal role in bacterial cell division [UniProt P16922]. It functions as a transpeptidase, catalyzing the cross-linking of peptidoglycan polymers to form the division septum during cytokinesis [PubMed: 31138571]. Because of its critical role in maintaining cell wall integrity during growth, PBP3 is a primary therapeutic target for several classes of beta-lactam antibiotics, including monobactams and cephalosporins [PubMed: 26169405]. Inhibition of PBP3 typically results in the formation of elongated, filamentous bacterial cells that eventually undergo lysis and death. In clinical settings, P. aeruginosa often develops resistance to these drugs through specific mutations in the PBP3 protein that decrease antibiotic binding affinity [PubMed: 30249619]. These mutations are frequently located in the transpeptidase domain or in loops near the active site, such as the Omega-loop or the 330-350 loop [PubMed: 29439971]. Consequently, PBP3 remains a focus of intense research for the development of novel inhibitors and combination therapies designed to bypass existing resistance mechanisms in multi-drug resistant strains [PubMed: 28223374].

Other names

FtsID-alanyl-D-alanine transpeptidaseSeptation protein FtsIPeptidoglycan glycosyltransferase/transpeptidasepbpCPBP-3

Inhibition of the transpeptidase activity of PBP3 prevents the cross-linking of peptidoglycan chains during cell wall synthesis, leading to the formation of filamentous cells and eventual osmotic lysis.