Penicillin-binding proteins of Helicobacter pylori (H. pylori PBPs)

Penicillin-binding proteins (PBPs) in Helicobacter pylori are a group of essential enzymes, including PBP1, PBP2, and PBP3, that catalyze the final stages of peptidoglycan synthesis, which is critical for maintaining the structural integrity of the bacterial cell wall (PubMed: 15930015). These proteins function primarily as transpeptidases and carboxypeptidases, facilitating the cross-linking of glycan strands that allow the bacterium to survive the acidic environment of the human stomach (UniProt: P56100). In the context of disease, H. pylori is a major causative agent of chronic gastritis, peptic ulcers, and gastric cancer, making its cell wall synthesis machinery a primary therapeutic target (NIH: NBK2441). PBPs are the molecular targets for beta-lactam antibiotics, most notably amoxicillin, which is a cornerstone of H. pylori eradication regimens. However, the emergence of resistance through point mutations in the PBP-encoding genes, particularly pbp1a, poses a significant challenge to clinical treatment efficacy (PubMed: 31635144). Understanding the structural variations of these proteins is vital for developing next-generation antimicrobial agents to overcome resistant strains.

Other names

PBPPeptidoglycan transpeptidaseD-alanyl-D-alanine carboxypeptidaseMurein hydrolasePBP1PBP2PBP3PBP4ponA

Beta-lactam antibiotics act as structural analogs of the D-alanyl-D-alanine terminus of peptidoglycan precursors, covalently binding to the active site of penicillin-binding proteins. This irreversible inhibition prevents the transpeptidation reaction required for cross-linking the peptidoglycan layer, leading to cell wall instability, osmotic lysis, and bacterial death (StatPearls, 2023; PubMed: 11519890).