Bacterial DNA gyrase and Beta-lactamase (DNA gyrase / BLA)

Bacterial DNA gyrase and beta-lactamase represent two critical but distinct protein targets in the fight against bacterial infections. DNA gyrase is a type II topoisomerase essential for managing DNA supercoiling during replication and transcription, primarily targeted by the fluoroquinolone class of antibiotics (Bush, 2018, PMID: 29408333). Beta-lactamases are enzymes produced by bacteria to hydrolyze the beta-lactam ring of antibiotics like penicillin, serving as a major mechanism of antimicrobial resistance (Bush & Bradford, 2016, PMID: 27325914). While they are separate biological entities, they are often discussed together in the context of dual-acting hybrid drugs or combination therapies designed to bypass resistance mechanisms (Hubschwerlen et al., 2003, PMID: 12930131). Targeting DNA gyrase halts bacterial proliferation by inducing DNA damage, whereas inhibiting beta-lactamase restores the efficacy of co-administered beta-lactam antibiotics. This multi-target approach is a key strategy in developing treatments for multidrug-resistant (MDR) Gram-negative and Gram-positive pathogens.

Other names

DNA topoisomerase (ATP-hydrolyzing)Type II topoisomerasePenicillinaseCephalosporinaseBeta-lactam hydrolaseESBL (Extended-spectrum beta-lactamase)

DNA gyrase inhibitors (e.g., fluoroquinolones) stabilize the covalent enzyme-DNA cleavage complex, leading to permanent double-strand breaks and bacterial cell death (PubMed: 24563074). Beta-lactamase inhibitors (e.g., avibactam) act as suicide substrates or reversible inhibitors that bind to the active site of beta-lactamases, preventing them from degrading beta-lactam antibiotics (PubMed: 27325914).