Penicillin-binding protein 1A, 1B, 2, and 3 (Pseudomonas aeruginosa) (PBPs)

Penicillin-binding proteins (PBPs) 1A, 1B, 2, and 3 are essential membrane-associated enzymes in Pseudomonas aeruginosa that catalyze the final steps of peptidoglycan biosynthesis, the structural backbone of the bacterial cell wall (UniProt: P18158, P18159, P15554, P15555). PBP1A and PBP1B are high-molecular-weight bifunctional enzymes possessing both transglycosylase and transpeptidase activities, whereas PBP2 and PBP3 are transpeptidases specialized in maintaining cell shape and facilitating septation during cell division, respectively (PubMed: 25261451). These proteins serve as the primary targets for beta-lactam antibiotics, which covalently bind to the active-site serine residue, thereby inhibiting the cross-linking of peptidoglycan strands. Inhibition of PBP3 typically leads to filamentation and cell death, while inhibition of PBP2 results in the formation of spherical cells (PubMed: 10449240). In Pseudomonas aeruginosa, these enzymes are critical for survival, and their modification or the production of beta-lactamases that degrade the targeting drugs are major drivers of clinical resistance (StatPearls: NBK545277). Consequently, these PBPs remain central to the development of novel antipseudomonal therapies, including siderophore-conjugated cephalosporins and beta-lactamase inhibitor combinations. The specific affinity of different antibiotics for these PBPs determines their morphological effects and bactericidal potency against this opportunistic pathogen.

Other names

PBP1A (mrcA)PBP1B (mrcB)PBP2 (pbpA)PBP3 (ftsI)Peptidoglycan glycosyltransferaseD-alanyl-D-alanine carboxypeptidaseTranspeptidase

Covalent inhibition of the transpeptidase domain of penicillin-binding proteins, preventing the cross-linking of peptidoglycan chains and leading to bacterial cell lysis.