Antibacterial action of quinolones: From target to network

Quinolones are widely used broad-spectrum antibacterials with incomplete elucidated mechanism of action. Here, molecular basis for the antibacterial action of quinolones, from target to network, is fully discussed and updated. Quinolones trap DNA gyrase or topoisomerase IV to form reversible drug-enzyme-DNA cleavage complexes, resulting in bacteriostasis. Cell death arises from chromosome fragmentation in protein synthesis-dependent or -independent pathways according to distinguished quinolone structures. In the former pathway, irreversible oxidative DNA damage caused by reactive oxygen species kills bacteria eventually. Toxin–antitoxin mazEF is triggered as an additional lethal action. Bacteria survive and develop resistance by SOS and other stress responses. Enlarged knowledges of quinolone actions and bacterial response will provide new targets for drug design and approaches to prevent bacterial resistance.

Graphical abstractQuinolone action network: the primary target, cell death pathway and bacterial response.Figure optionsDownload full-size imageDownload as PowerPoint slideHighlights► The history of discovering the primary targets of quinolones is described in details. ► The latest crystal structures of quinolone-type IIA topoisomerase–DNA complexes are updated. ► The network and pathway of quinolone action are proposed. ► The bacterial responses to quinolone stress are reviewed.