Bacterial class A beta-lactamase (Class A BL)

Bacterial class A beta-lactamases are a prominent group of enzymes that confer resistance to a wide range of beta-lactam antibiotics, including penicillins, cephalosporins, and carbapenems (Bush K, Jacoby GA, 2010, PMID: 20008565). These enzymes utilize a conserved active-site serine residue to nucleophilically attack and hydrolyze the four-membered beta-lactam ring, rendering the antibiotic ineffective (Ambler RP, 1980, PMID: 6991337). Class A enzymes include clinically significant variants such as TEM, SHV, CTX-M, and the highly problematic Klebsiella pneumoniae carbapenemase (KPC) (Papp-Wallace KM, et al., 2011, PMID: 21464367). They are primarily found in Gram-negative bacteria and are often encoded on mobile genetic elements like plasmids, facilitating rapid spread between species (Drawz SM, Bonomo RA, 2010, PMID: 20065326). To combat this resistance mechanism, clinicians use beta-lactamase inhibitors like clavulanic acid or avibactam in combination with antibiotics to protect the drug from degradation (Bush K, 2018, PMID: 29439114). Understanding the structural and functional diversity of these enzymes is critical for the development of next-generation antimicrobial therapies.

Other names

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

Beta-lactamase inhibitors function by binding to the active site of the enzyme, typically through a covalent interaction with the catalytic serine residue (suicide inhibition) or through high-affinity reversible binding, which prevents the enzyme from hydrolyzing the beta-lactam ring of co-administered antibiotics (Drawz SM, Bonomo RA, 2010, PMID: 20065326).