Acinetobacter baumannii Penicillin-Binding Protein 3 (PBP3) (PBP3)

Acinetobacter baumannii Penicillin-Binding Protein 3 (PBP3) is an essential enzyme involved in the final stages of peptidoglycan biosynthesis, specifically during bacterial cell division (septation) [1, 11]. As a high-molecular-mass Class B PBP, it functions as a DD-transpeptidase that catalyzes the cross-linking of peptidoglycan strands, which is critical for maintaining the structural integrity of the bacterial cell wall [11, 13]. PBP3 is a primary therapeutic target for several classes of beta-lactam antibiotics, including carbapenems, cephalosporins, and monobactams [1, 6]. Notably, the beta-lactamase inhibitor sulbactam exhibits unique intrinsic antibacterial activity against A. baumannii by binding directly to PBP3, a property not typically seen in other Gram-negative pathogens [2, 3, 5]. Resistance to these treatments often arises through mutations in the ftsI gene encoding PBP3 or through the production of beta-lactamases that degrade the antibiotics before they can reach the target [5, 9, 14]. Recent drug development efforts, such as the combination of sulbactam and durlobactam, specifically leverage the high affinity of these agents for PBP3 to overcome multi-drug resistant (MDR) A. baumannii infections [5, 9]. Understanding the structural and functional nuances of A. baumannii PBP3 is vital for the design of next-generation antibiotics capable of bypassing existing resistance mechanisms [6, 12].

Other names

PBP3FtsISeptal peptidoglycan synthaseDD-transpeptidasePenicillin-binding protein 3

Covalent inhibition of the transpeptidase domain of PBP3, preventing the cross-linking of peptidoglycan strands during cell wall synthesis, which leads to bacterial cell lysis and death [1, 2, 11].