Class A plasmid-mediated β-lactamase (Class A β-lactamase)

Class A plasmid-mediated β-lactamases are a diverse group of serine-based enzymes that catalyze the hydrolysis of the β-lactam ring in various antibiotics, including penicillins and cephalosporins (Ambler, 1980). These enzymes are primarily encoded on plasmids, which allows for their rapid horizontal transfer between bacterial species, significantly contributing to the global spread of antimicrobial resistance (Bush & Jacoby, 2010). Major families within this class include TEM, SHV, and the extended-spectrum β-lactamases (ESBLs) like CTX-M, as well as carbapenemases such as KPC (Bush, 2018). Their presence in pathogens like Klebsiella pneumoniae and Escherichia coli often leads to treatment failure in infections ranging from urinary tract infections to life-threatening sepsis (Pitout & Laupland, 2008). To overcome this resistance, these enzymes are targeted by β-lactamase inhibitors such as clavulanic acid, tazobactam, and newer agents like avibactam and vaborbactam (Drawz & Bonomo, 2010). These inhibitors work by binding to the active-site serine residue, thereby preventing the enzyme from degrading co-administered β-lactam antibiotics (Tooke et al., 2019). The continuous evolution of these enzymes, including the emergence of inhibitor-resistant variants, remains a major challenge in infectious disease management (Bonomo, 2017).

Other names

Ambler Class A β-lactamaseSerine β-lactamaseTEM-type β-lactamaseSHV-type β-lactamaseCTX-M-type β-lactamaseKPC-type β-lactamaseExtended-spectrum β-lactamase (ESBL)PenicillinaseCephalosporinase

Inhibition of the enzyme's catalytic activity through covalent binding (suicide inhibition) or non-covalent interaction, preventing the hydrolysis of co-administered β-lactam antibiotics (Drawz & Bonomo, 2010; Tooke et al., 2019).