Penicillin-binding proteins (Streptococcus pneumoniae) (PBPs)

Penicillin-binding proteins (PBPs) are a group of essential enzymes in Streptococcus pneumoniae responsible for the final stages of peptidoglycan biosynthesis, which is the primary component of the bacterial cell wall (Zapun et al., 2008, PMID: 18214377). These proteins, categorized into high-molecular-weight (Class A and B) and low-molecular-weight (Class C) types, catalyze the transglycosylation and transpeptidation reactions necessary for cell wall cross-linking and structural integrity (Hakenbeck et al., 2012, PMID: 22411030). In S. pneumoniae, there are six distinct PBPs: 1a, 1b, 2a, 2b, 2x, and 3, each playing specific roles in cell division and morphogenesis (UniProt, P0A4G2). PBPs are the primary therapeutic targets for beta-lactam antibiotics, such as penicillins and cephalosporins, which mimic the natural substrate and acylate the enzyme's active site (StatPearls, NBK551659). Inhibition of these enzymes leads to the cessation of cell wall synthesis, triggering autolytic enzymes and resulting in bacterial cell death. Clinical resistance in S. pneumoniae is frequently driven by the acquisition of mosaic pbp genes through horizontal gene transfer, which encode PBP variants with significantly reduced affinity for beta-lactam drugs (Chesnel et al., 2003, PMID: 12644490).

Other names

DD-transpeptidaseDD-carboxypeptidasePeptidoglycan synthasePBP1aPBP1bPBP2aPBP2bPBP2xPBP3

Beta-lactam antibiotics act as structural analogs of the D-alanyl-D-alanine terminus of peptidoglycan precursors, covalently binding to the active site serine of PBPs (StatPearls, NBK551659). This irreversible inhibition prevents the transpeptidation reaction required for cross-linking peptidoglycan chains, resulting in a weakened cell wall and subsequent bacterial lysis due to osmotic pressure (Zapun et al., 2008, PMID: 18214377).