DNA Topoisomerases as Targets for Antibacterial Agents

  • Hiroshi HiasaEmail author
Part of the Methods in Molecular Biology book series (MIMB, volume 1703)


DNA topoisomerases are proven therapeutic targets of antibacterial agents. Quinolones, especially fluoroquinolones, are the most successful topoisomerase-targeting antibacterial drugs. These drugs target type IIA topoisomerases in bacteria. Recent structural and biochemical studies on fluoroquinolones have provided the molecular basis for both their mechanism of action, as well as the molecular basis of bacterial resistance. Due to the development of drug resistance, including fluoroquinolone resistance, among bacterial pathogens, there is an urgent need to discover novel antibacterial agents. Recent advances in topoisomerase inhibitors may lead to the development of novel antibacterial drugs that are effective against fluoroquinolone-resistant pathogens. They include type IIA topoisomerase inhibitors that either interact with the GyrB/ParE subunit or form nick-containing ternary complexes. In addition, several topoisomerase I inhibitors have recently been identified. Thus, DNA topoisomerases remain important targets of antibacterial agents.

Key words

Aminocoumarin Antibacterial drugs DNA gyrase Fluoroquinolone Topoisomerase I Topoisomerase IV Topoisomerase poison 



I would like to thank Lisa Oppegard for her contribution and critical comments on the manuscript, Fang Li for invaluable discussion, and Justine Delgado for preparation of Fig. 1 and critical comments on the manuscript. Studies from my laboratory were supported in part by National Institutes of Health grants GM59465, AI087671, and a fellowship from SmithKline Beecham Pharmaceuticals.


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© Springer Science+Business Media, LLC 2018

Authors and Affiliations

  1. 1.Department of PharmacologyUniversity of Minnesota Medical SchoolMinneapolisUSA

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