Penicillin-binding proteins 1a, 1b, 2, and 3 of Klebsiella pneumoniae (K. pneumoniae PBP1a/1b/2/3)

Penicillin-binding proteins (PBPs) in Klebsiella pneumoniae are essential membrane-associated enzymes that catalyze the final steps of peptidoglycan biosynthesis, a process vital for maintaining the structural integrity and shape of the bacterial cell wall [1, 3]. This specific group includes PBP1a and PBP1b, which are bifunctional enzymes with both transglycosylase and transpeptidase activities involved in cell wall elongation, as well as PBP2 and PBP3, which are monofunctional transpeptidases required for maintaining rod shape and forming the division septum, respectively [1, 4]. These proteins are the primary therapeutic targets for beta-lactam antibiotics, including penicillins, cephalosporins, and carbapenems [2]. The drugs act as substrate analogs, covalently binding to the active-site serine of the PBPs and irreversibly inhibiting their transpeptidase activity [2, 3]. This inhibition disrupts the cross-linking of the peptidoglycan layer, leading to cell wall instability, morphological changes such as filamentation or spheroplast formation, and ultimately bacterial death through osmotic lysis [3]. In Klebsiella pneumoniae, a major human pathogen, the efficacy of drugs targeting these PBPs is frequently challenged by the production of beta-lactamases and, occasionally, by mutations within the PBPs that reduce antibiotic affinity [2, 4].

Other names

PBPsMurein transpeptidasesPeptidoglycan synthasesftsI (PBP3)mrdA (PBP2)mrcA (PBP1a)mrcB (PBP1b)D-alanyl-D-alanine carboxypeptidases

Covalent 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 lysis [1, 2].