Quinolone

Quinolones are synthetic antibacterial agents that exert bactericidal activity by targeting the bacterial type II topoisomerases DNA gyrase and topoisomerase IV, two enzymes essential for DNA replication, chromosome segregation, and maintenance of DNA topology^[1][2]. Mechanistically, quinolones stabilize enzyme-DNA cleavage complexes and block DNA strand passage catalysis, thereby arresting DNA replication and generating DNA damage that contributes to bacterial cell death^[1][3]. The key biological process affected by quinolone exposure is bacterial DNA metabolism, including DNA replication, supercoiling control, and chromosome decatenation, which are coordinated by DNA gyrase and topoisomerase IV during cell division^[2][4]. In bacterial infection models and clinical antimicrobial therapy, inhibition of these enzymes underlies the broad-spectrum activity of quinolone antibiotics against diverse Gram-negative and Gram-positive pathogens^[1][5]. Compared with the related isoform DNA gyrase, topoisomerase IV primarily mediates chromosome decatenation, and the relative contribution of each target to quinolone susceptibility varies among bacterial species^[2][5][6]. This distinction is particularly important because quinolones can display different target preferences, with DNA gyrase often representing the primary target in many Gram-negative bacteria and topoisomerase IV frequently contributing more substantially in Gram-positive organisms^[5][6]. For experimental applications, quinolones remain widely used chemical probes for investigating bacterial chromosome dynamics, topoisomerase function, and mechanisms of antimicrobial resistance^[1][3]. Resistance commonly arises through mutations affecting DNA gyrase or topoisomerase IV and through mechanisms that reduce intracellular drug accumulation, making quinolone-topoisomerase interactions a continuing focus of antibacterial drug discovery and resistance research^[1][7][8].