Penicillin-binding protein 2 (PBP 2) (PBP 2)

Penicillin-binding protein 2 (PBP 2) is an essential high-molecular-weight class B enzyme in Pseudomonas aeruginosa that plays a critical role in cell wall synthesis and the maintenance of rod-shaped bacterial morphology [2, 6]. It functions as a transpeptidase, catalyzing the cross-linking of peptidoglycan precursors within the periplasmic space to ensure the structural integrity of the cell wall [6, 9]. While PBP 3 is often considered the primary target for many antipseudomonal beta-lactams, PBP 2 is the specific target of the amidinopenicillin mecillinam and is also inhibited with high affinity by carbapenems such as imipenem [4, 7]. Inhibition of PBP 2 leads to the formation of spherical cells (spheroplasts), which can result in bacterial lysis or significantly reduced fitness [2, 3]. In the face of rising multidrug resistance, PBP 2 has emerged as a key target for novel diazabicyclooctane enhancers like zidebactam, which synergize with other beta-lactams by specifically inactivating this protein [7]. Resistance to drugs targeting PBP 2 is primarily driven by non-target mechanisms, including the loss of the OprD porin, upregulation of efflux pumps like MexAB-OprM, and the hyperproduction of the AmpC beta-lactamase [1, 11, 15].

Other names

PBP 2PBP2mrdApbpAPenicillin-binding protein 2

Inhibition of peptidoglycan transpeptidation by covalent binding to the active site serine (S327), leading to cell wall instability and morphological transformation from rods to spheres [6, 7].