Helicobacter pylori penicillin-binding proteins (PBPs)

Helicobacter pylori penicillin-binding proteins (PBPs) are a group of essential membrane-associated enzymes involved in the biosynthesis and remodeling of the bacterial cell wall [3, 6]. These proteins, which include high-molecular-weight (PBP1, PBP2, PBP3) and low-molecular-weight varieties, catalyze the transpeptidation and glycosyltransferase reactions necessary for cross-linking peptidoglycan strands [3, 9, 14]. This process is critical for maintaining the structural integrity and shape of the bacterium, especially within the harsh acidic environment of the human stomach [6, 13]. PBPs are the primary therapeutic targets for beta-lactam antibiotics, such as amoxicillin, which is a key component of multi-drug regimens used to eradicate H. pylori infections [3, 7, 9]. H. pylori is a major human pathogen linked to chronic gastritis, peptic ulcers, and gastric adenocarcinoma [5, 12, 17]. The interaction between beta-lactams and PBPs involves the antibiotic binding to the enzyme's active site, effectively halting cell wall synthesis and leading to bacterial lysis [3, 14]. However, the emergence of antibiotic resistance, primarily driven by point mutations in the PBP genes (especially pbp1a), poses a significant challenge to clinical eradication efforts [1, 2, 8, 15]. Monitoring these genetic alterations has become a vital strategy for predicting treatment outcomes and managing multidrug-resistant H. pylori strains [10, 17, 19].

Other names

Penicillin-binding protein 1A (PBP1A) [3, 9]Penicillin-binding protein 2 (PBP2) [1, 10]Penicillin-binding protein 3 (PBP3) [1, 10]HP0597 [1, 8]HP1556 [1, 10]HP1565 [1, 10]Transpeptidase [6, 14]Peptidoglycan glycosyltransferase [3, 14]

Inhibition of bacterial cell wall synthesis by binding to and inactivating transpeptidase enzymes (PBPs), preventing the cross-linking of peptidoglycan strands [3, 14].