Robert J. Kerns

TL;DR: This review describes the development of the quinolones as antibacterials, the structure and function of gyrase and topoisomerase IV, and the mechanistic basis for quInolone action against their enzyme targets, and suggests approaches to designing new drugs that display improved activity against resistant strains.

TL;DR: In the present minireview, cell death is considered through a two-part “poison” hypothesis in which the quinolones form reversible drug-topoisomerase-DNA complexes that subsequently lead to several types of irreversible (lethal) damage.

TL;DR: Quinolone resistance arises stepwise through selective amplification of mutants when drug concentrations are above the MIC and below the MPC, as observed with static agar plate assays, dynamic in vitro systems, and experimental infection of rabbits.

TL;DR: Interestingly, the structural data revealed few differences in fluoroquinolone–enzyme contacts from drugs that have very different activities against Mtb, and point to new approaches for developing quinolone-class compounds that have increased potency against MtB and the ability to overcome resistance.

TL;DR: Functional evidence for the existence of the water-metal ion bridge is provided, it is confirmed that the serine and glutamic acid residues anchor the bridge, and it is demonstrated that the bridge is the primary conduit for interactions between clinically relevant quinolones and topoisomerase IV are provided.