4-Quinolones and the Physiology of DNA Gyrase

This chapter discusses 4-quinolones and the physiology of DNA gyrase. The 4-quinolones are potent antibacterial agents that interfere with a wide variety of DNA-related processes. It became clear from biochemical studies that the quinolones trap gyrase on DNA, and this made the drugs useful for studying intracellular gyrase action. The chapter reviews the role of gyrase in the control of DNA supercoiling. Then, it explains how the quinolones, by interacting with gyrase, create lesions in DNA and disrupt bacterial growth. Strong interaction sites have been identified; by placing these near promoters in plasmids, it may be possible to examine how gyrase influences transcription. Locating cleavage complexes may help to better understand how chromosomal activities such as transcription affect gyrase-DNA interactions and DNA supercoiling. The earliest biochemical event in the cell is probably the formation of drug-gyrase-DNA complexes in which the DNA is broken. These complexes block chromosome replication. Although both double-stranded DNA breaks and uncoupling of DNA replication from cell wall synthesis can be lethal, additional protein synthesis is required for the older quinolones to kill bacterial cells.