Our Evolving Understanding of the Mechanism of Quinolones
Inserm U1001, Université Paris Descartes, Sorbonne Paris Cité, Faculté de Médecine Paris Descartes, 75014 Paris, France
Institute for Medical Engineering & Science, Department of Biological Engineering, and Synthetic Biology Center, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
Infectious Disease and Microbiome Program, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA
Department of Life Sciences, Centre National de la Recherche Scientifique, 75016 Paris, France
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Antibiotics 2018, 7(2), 32; https://doi.org/10.3390/antibiotics7020032
Received: 9 February 2018 / Revised: 30 March 2018 / Accepted: 4 April 2018 / Published: 8 April 2018
(This article belongs to the Special Issue Bacterial DNA Replication and Replication Inhibitors)
The maintenance of DNA supercoiling is essential for the proper regulation of a plethora of biological processes. As a consequence of this mode of regulation, ahead of the replication fork, DNA replication machinery is prone to introducing supercoiled regions into the DNA double helix. Resolution of DNA supercoiling is essential to maintain DNA replication rates that are amenable to life. This resolution is handled by evolutionarily conserved enzymes known as topoisomerases. The activity of topoisomerases is essential, and therefore constitutes a prime candidate for targeting by antibiotics. In this review, we present hallmark investigations describing the mode of action of quinolones, one of the antibacterial classes targeting the function of topoisomerases in bacteria. By chronologically analyzing data gathered on the mode of action of this imperative antibiotic class, we highlight the necessity to look beyond primary drug-target interactions towards thoroughly understanding the mechanism of quinolones at the level of the cell.