Penicillin-binding proteins in Acinetobacter baumannii (PBPs)

Penicillin-binding proteins (PBPs) are a group of essential enzymes in Acinetobacter baumannii that catalyze the final steps of peptidoglycan biosynthesis, the structural backbone of the bacterial cell wall (NIH, 2022; NIH, 2011). These proteins are categorized into high-molecular-mass (HMM) PBPs, which possess transpeptidase and sometimes transglycosylase activities, and low-molecular-mass (LMM) PBPs, which typically function as carboxypeptidases or endopeptidases (NIH, 2022; NIH, 2011). In A. baumannii, specific PBPs such as PBP3 (FtsI) are indispensable for cell division, while others like PBP1a and PBP2 contribute to cell elongation and structural integrity (NIH, 2022; ASM, 2021). PBPs are the primary targets for beta-lactam antibiotics, including carbapenems and cephalosporins, which covalently bind to the active site of the transpeptidase domain to inhibit cell wall cross-linking (NIH, 2022; NIH, 2011). This inhibition leads to the loss of cell wall integrity, resulting in bacterial cell lysis and death (NIH, 2022; NIH, 2011). Resistance to these drugs in A. baumannii is a major clinical challenge, often mediated by PBP modifications that reduce drug affinity, decreased PBP expression, or the production of beta-lactamases (NIH, 2011; ASM, 2023). Consequently, PBPs remain a focal point for the development of novel antimicrobial strategies, such as the sulbactam-durlobactam combination, to combat multidrug-resistant infections (NIH, 2025; MDPI, 2025). Understanding the specific roles and interactions of different PBPs is crucial for overcoming the high levels of resistance observed in this opportunistic pathogen (NIH, 2022; ASM, 2021).

Other names

PBPsPeptidoglycan synthasesTranspeptidasesCarboxypeptidasesTransglycosylasesPBP1a (mrcA)PBP1b (mrcB)PBP2PBP3 (ftsI)PBP5PBP7/8 (pbpG)

Inhibition of the transpeptidase domain of penicillin-binding proteins, which prevents the cross-linking of peptidoglycan chains in the bacterial cell wall, leading to cell wall instability and osmotic lysis (NIH, 2022; NIH, 2011).