Resistance Mechanisms in Various Bacteria Against DNA Gyrase Inhibitors: A Concise Review

Abstract

DNA gyrase, a bacterial type 2 isomerase is a critical enzyme to maintain DNA supercoiling during replication and transcription. DNA gyrase inhibitors have been widely used to treat serious infections, bearing great importance in clinical settings. Multiple inhibitors, including fluoroquinolones (FQs) and other gyrase inhibitors stabilizes the DNA-enzyme cleavage complex and halt DNA re-ligation. The widespread use of these inhibitors in the form of antibiotics introduces antimicrobial resistance (AMR). Emerging evidence indicates that resistance to DNA gyrase inhibitors is driven by a dynamic interplay of genetic mutations, adaptive cellular responses, and mobile genetic elements (MGEs). Across Gram-negative and Gram-positive pathogens, as well as in acid-fast bacteria, distinct yet overlapping molecular strategies have evolved to reduce drug susceptibility and promote survival under antimicrobial pressure. These bacterial species are adapted to act mechanistically, hence becoming resistant to the antibiotics. This review explores the molecular basis of resistance to DNA gyrase inhibitors in clinically significant bacterial pathogens, highlighting how evolutionary adaptation and selective pressure continue to reshape the landscape of antibacterial therapy. Understanding these processes is crucial for informing future treatment strategies and mitigating the growing threat of resistant infections.