Class C and Class D beta-lactamases (OXA and ADC subtypes) (OXA and ADC beta-lactamases)

Class C and Class D beta-lactamases, specifically the Acinetobacter-derived cephalosporinases (ADC) and oxacillinases (OXA), are critical enzymes that mediate antibiotic resistance in Gram-negative bacteria such as Acinetobacter baumannii (PubMed: 25246706). These enzymes function by hydrolyzing the beta-lactam ring of various antibiotics, including cephalosporins and carbapenems, thereby neutralizing their bactericidal effects (PubMed: 28196865). The OXA family is particularly diverse, with many variants functioning as carbapenem-hydrolyzing class D beta-lactamases (CHDLs), which are a leading cause of carbapenem resistance globally (PubMed: 24277854). ADC enzymes are chromosomally encoded cephalosporinases that, when overexpressed due to genetic insertion sequences, confer high-level resistance to extended-spectrum cephalosporins (PubMed: 16148278). Therapeutic strategies targeting these enzymes involve the use of beta-lactamase inhibitors like durlobactam, which are often paired with beta-lactams like sulbactam (FDA: Xacduro Label). These inhibitors work by forming a stable, covalent complex with the active-site serine of the enzyme, preventing it from degrading the antibiotic and restoring the drug's efficacy against multidrug-resistant pathogens (PubMed: 33851814).

Other names

OxacillinasesAcinetobacter-derived cephalosporinasesClass D serine beta-lactamasesClass C serine beta-lactamasesCarbapenem-hydrolyzing class D beta-lactamases (CHDLs)AmpC-type beta-lactamases

Covalent inhibition of the active-site serine residue within the beta-lactamase enzyme, preventing the hydrolysis of beta-lactam antibiotics.