Penicillin-binding protein 2 (PBP2) and other penicillin-binding proteins (PBPs) in Acinetobacter baumannii (PBPs (A. baumannii))

Penicillin-binding proteins (PBPs) in Acinetobacter baumannii are essential enzymes that catalyze the final steps of peptidoglycan biosynthesis, which is vital for maintaining the bacterial cell wall's structural integrity (Sauvage et al., 2008; PMID: 18218613). These proteins are categorized into high-molecular-weight (HMW) PBPs, such as PBP1a, PBP1b, PBP2, and PBP3, and low-molecular-weight (LMW) PBPs. PBP2 (encoded by mrdA) is primarily responsible for maintaining the rod shape of the bacterium, while PBP3 (encoded by ftsI) is crucial for cell division and septum formation (Higgins et al., 2004; PMID: 15254023). These enzymes are the primary targets for beta-lactam antibiotics, which act as substrate analogs and covalently bind to the active site serine, thereby inhibiting the transpeptidation reaction (Papp-Wallace et al., 2012; PMID: 22006003). In A. baumannii, sulbactam exhibits unique intrinsic activity by specifically targeting PBP1 and PBP3, leading to bacterial death (Penwell et al., 2015; PMID: 25583714). Resistance to these drugs often arises through mutations in the PBP genes that reduce drug affinity or through the production of beta-lactamases that degrade the antibiotics before they reach the PBPs. Consequently, A. baumannii has become a significant cause of healthcare-associated infections, including pneumonia and bacteremia, particularly in intensive care settings. Modern therapeutic strategies, such as the combination of sulbactam with the beta-lactamase inhibitor durlobactam, aim to protect the drug's ability to bind to these essential PBPs in multi-drug resistant strains (Karlowsky et al., 2023; PMID: 37154717).

Other names

PBPsPeptidoglycan transpeptidasesmrdA (PBP2)ftsI (PBP3)ponA (PBP1a)mrcB (PBP1b)D-alanyl-D-alanine carboxypeptidasesPenicillin-binding protein 2Penicillin-binding protein 3Penicillin-binding protein 1aPenicillin-binding protein 1b

Inhibition of the transpeptidase domain of penicillin-binding proteins, preventing the cross-linking of peptidoglycan chains in the bacterial cell wall, leading to cell lysis.