Plasmid-mediated beta-lactamase (PMBL) (PMBL)

Plasmid-mediated beta-lactamases are enzymes produced by bacteria that confer resistance to beta-lactam antibiotics, including penicillins, cephalosporins, and carbapenems, by hydrolyzing the antibiotic's cyclic amide bond (StatPearls, NBK554444). These enzymes are encoded on plasmids, which are mobile genetic elements that facilitate the rapid horizontal transfer of resistance genes between different bacterial species and strains (CDC, 2023). They are categorized into four Ambler classes (A, B, C, and D) based on their molecular structure and catalytic mechanism, utilizing either a serine-based or a zinc-dependent active site (Nature Reviews Microbiology, 2010). Clinically significant examples include extended-spectrum beta-lactamases (ESBLs) and carbapenemases such as KPC and NDM-1, which are major drivers of multidrug resistance in Gram-negative pathogens (PubMed, 30639111). Therapeutic intervention typically involves the use of beta-lactamase inhibitors, such as clavulanic acid, avibactam, or vaborbactam, which are administered in combination with beta-lactam antibiotics to protect them from enzymatic degradation (PubChem). The ongoing evolution of these enzymes continues to challenge the efficacy of existing antimicrobial therapies and necessitates the development of next-generation inhibitors (NIH).

Other names

Plasmid-encoded beta-lactamaseExtended-spectrum beta-lactamaseESBLCarbapenemaseSerine beta-lactamaseMetallo-beta-lactamase

Beta-lactamase inhibition; these drugs act as suicide substrates or reversible inhibitors that bind to the enzyme's active site, preventing it from degrading co-administered beta-lactam antibiotics.