Our Evolving Understanding of the Mechanism of Quinolones
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antibiotics-07-00032.pdf
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261.76 KB
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Author(s)
Gutierrez, Arnaud
Stokes, Jonathan M.
Matic, Ivan
Stokes, Jonathan
Date Issued
April 2018
Journal
Antibiotics
Publisher
MDPI AG
Citation
Gutierrez, Arnaud et al. "Our Evolving Understanding of the Mechanism of Quinolones." Antibiotics 7, 2 (April 2018): 32 © 2018 The Authors
Version
Final published version
Abstract
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. Keywords: antibiotics; quinolones; topoisomerases; DNA replication; DNA supercoiling
MIT Department
Massachusetts Institute of Technology. Institute for Medical Engineering & Science
Massachusetts Institute of Technology. Synthetic Biology Center
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Creative Commons Attribution
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DOI of Published Version
https://doi.org/10.3390/antibiotics7020032
