betalactamase

Beta-lactamase is an enzyme produced by bacteria that hydrolyzes the beta-lactam ring of many antibiotics, including penicillins and cephalosporins, thereby inactivating the drug. Beta-lactamase production is a major mechanism of resistance and has spread across many pathogens due to antibiotic pressure and mobile genetic elements.

Mechanism: these enzymes cleave the amide bond in the four-membered beta-lactam ring. Serine beta-lactamases use an active-site serine to form a covalent acyl-enzyme intermediate, while metallo-beta-lactamases rely on zinc to activate a water molecule that hydrolyzes the ring. Some enzymes broaden their activity to newer drugs, contributing to extended-spectrum beta-lactamases and carbapenemases.

Classification: beta-lactamases are traditionally grouped into Ambler classes A through D. Class A, C, and D are serine beta-lactamases; Class B comprises metallo-beta-lactamases. Clinically important subsets include ESBLs (e.g., TEM, SHV, CTX-M families), AmpC beta-lactamases, and carbapenemases (e.g., KPC, NDM, VIM, IMP, OXA-48).

Clinical impact: production confers resistance to many penicillins and cephalosporins, and carbapenemases greatly limit treatment options. Detection relies on phenotypic tests (colorimetric nitrocefin test, disk diffusion with inhibitors) and molecular methods (PCR).

Therapy and surveillance: beta-lactamase inhibitors such as clavulanic acid, sulbactam, and tazobactam restore activity of some combinations; newer inhibitors (avibactam, relebactam, vaborbactam) expand coverage against certain beta-lactamases. Ongoing stewardship and infection-control measures address the spread of resistant enzymes in Gram-negative pathogens.