Book chapter
Bacterial Type II Topoisomerases and Target-Mediated Drug Resistance
Antimicrobial Resistance in the 21st Century, pp.507-529
Emerging Infectious Diseases of the 21st Century, Springer International Publishing
11/11/2018
DOI: 10.1007/978-3-319-78538-7_16
Abstract
Fluoroquinolones are one of the most widely prescribed classes of broad-spectrum antibacterials currently in clinical use. These drugs kill bacteria by increasing DNA strand breaks generated by the type II topoisomerases, gyrase and topoisomerase IV. Despite the importance of fluoroquinolones in the treatment of bacterial infections, their usefulness is being diminished by the rise of drug resistance. The most common and clinically relevant form of fluoroquinolone resistance is target-mediated, which is caused by specific mutations in gyrase and topoisomerase IV. Although these mutations were first identified over 30 years ago, the mechanism by which they cause resistance has only recently been established. This knowledge has contributed greatly to our understanding of how fluoroquinolones interact with their enzyme targets and has suggested mechanisms for overcoming resistance. In order to more fully describe target-mediated fluoroquinolone resistance, this article will provide background on the drug class, discuss how gyrase and topoisomerase IV function, describe the basis for fluoroquinolone-enzyme interactions, and discuss how altering these interactions leads to resistance. Finally, new approaches to overcoming target-mediated fluoroquinolone resistance will be discussed.
Details
- Title: Subtitle
- Bacterial Type II Topoisomerases and Target-Mediated Drug Resistance
- Creators
- Elizabeth G. Gibson - Vanderbilt University School of MedicineRachel E. Ashley - Vanderbilt UniversityRobert J. Kerns - University of IowaNeil Osheroff - Vanderbilt University
- Resource Type
- Book chapter
- Publication Details
- Antimicrobial Resistance in the 21st Century, pp.507-529
- Publisher
- Springer International Publishing; Cham
- Series
- Emerging Infectious Diseases of the 21st Century
- DOI
- 10.1007/978-3-319-78538-7_16
- Language
- English
- Date published
- 11/11/2018
- Academic Unit
- Pharmaceutical Sciences and Experimental Therapeutics; Medicinal and Natural Products Chemistry
- Record Identifier
- 9984366402102771
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