Penicillin-binding protein 3 (Salmonella) (PBP3)

Penicillin-binding protein 3 (PBP3), also known as FtsI, is an essential enzyme in Salmonella species that plays a critical role in bacterial cell division [1]. It is a transpeptidase responsible for cross-linking peptidoglycan strands specifically at the division septum, a process necessary for the formation of new cell walls during cytokinesis [1, 2]. Because of its vital role in maintaining bacterial structural integrity, PBP3 is a primary target for several classes of beta-lactam antibiotics, including monobactams like aztreonam and various cephalosporins [2, 3]. When these drugs bind to PBP3, they inhibit its enzymatic activity, causing the bacteria to form long, non-dividing filaments that eventually undergo lysis [2]. In clinical practice, PBP3 is a key target for treating infections caused by Salmonella enterica, including typhoid fever and non-typhoidal salmonellosis [3]. However, the therapeutic utility of targeting PBP3 is increasingly threatened by the emergence of mutations in the ftsI gene, which can reduce the binding affinity of antibiotics and lead to multi-drug resistance [3, 4]. (References: [1] UniProtKB P0A2E5; [2] Spratt, B. G., PNAS 1975; [3] Aghazadeh, H., et al., J Med Microbiol 2019; [4] Li, X. Z., et al., Antibiotics 2023).

Other names

FtsISeptum formation protein FtsIPeptidoglycan D-amino acid transpeptidasePBP-3D-alanyl-D-alanine carboxypeptidase

Inhibition of the transpeptidase activity of PBP3, which prevents the cross-linking of peptidoglycan subunits during cell wall synthesis, leading to filamentation and bacterial cell death.