Penicillin-binding proteins (Helicobacter pylori) (PBPs)

Penicillin-binding proteins (PBPs) in Helicobacter pylori are a group of essential membrane-bound enzymes responsible for the assembly and maintenance of the bacterial peptidoglycan cell wall [1, 3]. These proteins, which include high-molecular-weight varieties like PBP1A, PBP2, and PBP3, catalyze critical transpeptidation and glycosyltransferase reactions that provide structural integrity to the bacterium [5, 9]. PBPs are the primary therapeutic targets for beta-lactam antibiotics, most notably amoxicillin, which is a cornerstone of H. pylori eradication therapy [2, 16]. By covalently binding to the active site of these enzymes, antibiotics inhibit cell wall synthesis, leading to osmotic lysis and bacterial death [2, 8]. However, the emergence of point mutations in PBP genes, particularly pbp1a, has led to a significant increase in amoxicillin resistance worldwide [7, 11]. This resistance poses a major challenge in clinical practice, as persistent H. pylori infection is a leading cause of chronic gastritis, peptic ulcers, and gastric adenocarcinoma [10, 20]. Consequently, monitoring PBP mutations has become an important strategy for predicting treatment outcomes and managing antibiotic resistance in infected patients [12, 16].

Other names

Penicillin-binding proteinPeptidoglycan transpeptidasePBP1APBP2PBP3HP0597HP1556HP1565ftsIpbp2

Beta-lactam antibiotics covalently bind to the active site serine of the PBP transpeptidase domain, mimicking the D-alanyl-D-alanine substrate. This inhibition prevents the cross-linking of peptidoglycan strands, weakening the bacterial cell wall and leading to osmotic lysis and cell death [2, 5].