Katie J. Aldred

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: 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.

TL;DR: 8-Methyl-quinazoline-2,4-dione was more potent than quinolones against wild-type topoisomerase IV and was equally efficacious, and maintained high potency and efficacy against the mutant enzymes, effectively inhibited DNA religation, and formed stable ternary complexes.

TL;DR: It is determined that an 8-methyl-moxifloxacin derivative induces high levels of stable cleavage complexes with WT gyrase and two common resistant enzymes, GyrAA90V and GyrAD94G.

TL;DR: A chemical biology approach was utilized to determine how quinazolinediones overcome quinolone resistance in Bacillus anthracis topoisomerase IV and three compounds are identified that display high activity against qu inolone-resistant B. anthracIS topoisomease IV but low activity against human topoisomersase IIα.