Gyrase and Topoisomerase IV as Targets for Antibacterial Drugs
Beyond their essential cellular functions, the bacterial type II topoisomerases, gyrase and topoisomerase IV, are targets for quinolone-based drugs. Quinolones are the most efficacious and broad-spectrum oral antibacterial agents currently in clinical use. Similar to the topoisomerase-targeted anticancer drugs, quinolones are topoisomerase II poisons that increase the levels of gyrase- and topoisomerase IV-DNA cleavage complexes. Both bacterial type II enzymes appear to be physiological targets of quinolones; however, the relative contributions of gyrase and topoisomerase IV to quinolone efficacy appear to be strain and drug specific. Initial resistance to quinolones usually results from specific point mutations in gyrase or topoisomerase IV. Recent models for quinolone-enzyme interactions may help to develop novel drugs that overcome resistance. Finally, a number of non-quinolone drugs display activity against gyrase and topoisomerase IV and are in development.
KeywordsQuinolone Resistance Torsional Stress Cleavage Complex Oxolinic Acid Multidrug Efflux Pump
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