Plasmid-mediated beta-lactamase (PMBL)

Plasmid-mediated beta-lactamases are enzymes produced by bacteria that confer resistance to beta-lactam antibiotics, including penicillins, cephalosporins, and carbapenems [1]. These enzymes are encoded on plasmids, which are mobile genetic elements that facilitate the rapid horizontal transfer of resistance genes between different bacterial species [2]. Functionally, they act by hydrolyzing the beta-lactam ring of the antibiotic, rendering the drug inactive before it can bind to its target penicillin-binding proteins [3]. This enzymatic activity is a primary driver of multidrug resistance in clinical settings, particularly among Enterobacteriaceae and other Gram-negative pathogens [1]. The classification of these enzymes includes serine-based classes (A, C, and D) and zinc-dependent metallo-beta-lactamases (Class B) [2]. To combat this resistance, pharmaceutical development focuses on beta-lactamase inhibitors like clavulanic acid, tazobactam, and newer agents like avibactam and vaborbactam [3]. These inhibitors are typically co-administered with a beta-lactam antibiotic to shield the antibiotic from degradation and restore its therapeutic activity [4]. The ongoing evolution of these enzymes, such as the emergence of carbapenemases, continues to pose a severe threat to global public health [2].

Other names

Plasmid-mediated β-lactamasePlasmid-encoded beta-lactamasePlasmid-borne beta-lactamaseExtended-spectrum beta-lactamase (ESBL)Plasmid-mediated AmpCCarbapenemase

Beta-lactamase inhibitors function by binding to the active site of the beta-lactamase enzyme, thereby preventing it from hydrolyzing the beta-lactam ring of co-administered antibiotics [3]. This binding can be irreversible (suicide inhibition), as seen with clavulanic acid and tazobactam, or reversible, as seen with newer non-beta-lactam inhibitors like avibactam and vaborbactam [4].