Bacterial class A serine beta-lactamase (Class A BLA)

Bacterial class A serine beta-lactamases are a diverse group of enzymes that represent a primary mechanism of antibiotic resistance in Gram-negative and some Gram-positive bacteria (Bush & Bradford, 2016). These enzymes function by hydrolyzing the four-membered beta-lactam ring of antibiotics such as penicillins, cephalosporins, and carbapenems, rendering them inactive before they can reach their target, the penicillin-binding proteins (Ambler, 1980). The catalytic mechanism involves a conserved serine residue that forms a covalent acyl-enzyme intermediate with the antibiotic (Drawz & Bonomo, 2010). Clinically significant members of this class include TEM, SHV, and CTX-M extended-spectrum beta-lactamases (ESBLs), as well as KPC carbapenemases, which significantly limit treatment options for serious infections (Bush, 2018). Therapeutic strategies involve the use of beta-lactamase inhibitors, such as clavulanic acid or avibactam, which bind to and disable the enzyme, thereby protecting the companion antibiotic from degradation (StatPearls, 2023). The rapid evolution and global dissemination of these enzymes via mobile genetic elements pose a significant challenge to modern medicine (PubMed, 2022).

Other names

Ambler class A beta-lactamaseSerine beta-lactamase class APenicillinaseExtended-spectrum beta-lactamase (ESBL)Klebsiella pneumoniae carbapenemase (KPC)

Inhibition of the enzyme's catalytic activity through covalent or non-covalent binding, preventing the hydrolysis of co-administered beta-lactam antibiotics (Drawz & Bonomo, 2010).