β-lactam

β-lactam antibiotics act on bacterial cell-wall biogenesis by covalently binding penicillin-binding proteins (PBPs), enzymes linked to peptidoglycan transpeptidation, growth, division, and cell-wall integrity^[1]. Mechanistically, β-lactams disrupt peptidoglycan cross-linking, and experimental work shows that they can induce lethal malfunctioning of the cell-wall synthesis and degradation cycle^[2]. In resistance models, bacteria reduce β-lactam activity through β-lactamases, altered PBPs, outer-membrane permeability changes, or alternative peptidoglycan cross-linking by L,D-transpeptidases^[1][3]. Compared with high-molecular-weight PBPs, which are essential transpeptidases, low-molecular-weight PBPs show less defined physiological roles but contribute to β-lactam resistance through mutation or altered abundance^[3]. Isoform-specific studies further show that PBP2a, PBP4, PBP5, PonA1, and PonA2 differ in affinity, structural behavior, and β-lactam inactivation capacity, making isoform selection critical for resistance-focused experiments^[4][5][6]. For experimental applications, β-lactamase inhibitors and potentiators support resistance-mechanism studies, while β-lactone probes and PbpP-based sensing models help analyze PBP binding, isoform selectivity, and β-lactam response pathways^[7][8][9].