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Eur J Med Chem. 2013 Aug;66:555-62. doi: 10.1016/j.ejmech.2013.01.057. Epub 2013 Mar 4.

Antibacterial action of quinolones: from target to network.

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1
National Reference Laboratory of Veterinary Drug Residues (HZAU) and MOA Key Laboratory for Detection of Veterinary Drug Residues in Foods, Huazhong Agricultural University, Wuhan, Hubei 430070, China.

Abstract

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.

KEYWORDS:

Bacterial response; Bacteriostatic action; Crystal structure; Lethal action; Primary target

PMID:
23528390
DOI:
10.1016/j.ejmech.2013.01.057
[Indexed for MEDLINE]
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