Penicillin-binding proteins: the master builders and breakers of bacterial cell walls and its interaction with β-lactam antibiotics

Penicillin-binding proteins (PBPs) have been the subject of analysis for over 40 years. These proteins play a crucial role in catalyzing peptidoglycan synthesis within bacteria, providing structural integrity and enabling them to withstand high intracellular pressures. PBPs are involved in peptidoglycan biosynthesis during cell wall elongation and septum formation. They are categorized into three classes: class A, class B, and class C. Class A PBPs have a dual function, acting as transpeptidases that cross-link glycan chains and transglycosylases that polymerize glycan strands. Some PBPs can hydrolyze peptide bonds connecting glycan strands (endopeptidation) or the terminal D-alanine of stem peptides (DD-carboxypeptidation). Class A and class B PBPs have distinct morphological roles, requiring specific protein localization and interactions with cellular components for shape determination. Mutations in PBPs are a major cause of multidrug-resistant (MDR) strains in pathogenic bacteria, posing challenges for infection control. The rapid spread of antibiotic resistance and the emergence of MDR strains raise concerns in bacterial infection treatment. Therefore, studying PBP allelic differentiation and mutations is crucial for research purposes. This review will discuss various types of PBPs, their mode of action, structural information about their domains, and the interaction of β-lactam antibiotics with wild-type and mutant PBPs. Understanding these aspects is essential for combating antibiotic resistance and developing effective treatments against bacterial infections.