Penicillin-binding protein 3 (Salmonella enterica) (PBP3)

Penicillin-binding protein 3 (PBP3), also known as FtsI, is an essential enzyme in Salmonella enterica required for the synthesis of the bacterial cell wall during division (UniProt: P0A2B5). It is a high-molecular-weight transpeptidase that specifically catalyzes the cross-linking of peptidoglycan polymers at the division septum, a process vital for forming the daughter cell walls (PubMed: 15576774). Because of its critical role in septation, PBP3 is a primary target for various beta-lactam antibiotics, particularly monobactams like aztreonam and third-generation cephalosporins (PubChem CID 57428). When these drugs bind to PBP3, they inhibit its enzymatic activity, leading to the cessation of cell division, the formation of long filamentous cells, and eventual osmotic lysis. In clinical practice, PBP3 is a key target for treating Salmonella-related diseases, including typhoid fever and invasive non-typhoidal salmonellosis (PubMed: 25307113). However, the emergence of resistance through mutations in the ftsI gene or the production of extended-spectrum beta-lactamases poses a significant challenge to the continued efficacy of drugs targeting this protein (PubMed: 31636131).

Other names

FtsISeptum formation protein FtsID-alanyl-D-alanine transpeptidase FtsIPeptidoglycan glycosyltransferase FtsIPBP-3

Covalent inhibition of the transpeptidase domain, which prevents the cross-linking of peptidoglycan strands during septum formation, leading to cell filamentation and lysis.