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Rifampicin Resistance: Fitness Costs and the Significance of Compensatory Evolution
Department of Medical Biochemistry and Microbiology / Box 582, Biomedical Center, Uppsala University, Husargatan 3, Uppsala 75423, Sweden
* Author to whom correspondence should be addressed.
Received: 1 February 2013; in revised form: 28 March 2013 / Accepted: 28 March 2013 / Published: 3 April 2013
Abstract: Seventy years after the introduction of antibiotic chemotherapy to treat tuberculosis, problems caused by drug-resistance in Mycobacterium tuberculosis have become greater than ever. The discovery and development of novel drugs and drug combination therapies will be critical to managing these problematic infections. However, to maintain effective therapy in the long-term and to avoid repeating the mistakes of the past, it is essential that we understand how resistance to antibiotics evolves in M. tuberculosis. Recent studies in genomics and genetics, employing both clinical isolates and model organisms, have revealed that resistance to the frontline anti-tuberculosis drug, rifampicin, is very strongly associated with the selection of fitness compensatory mutations in the different subunits of RNA polymerase. This mode of resistance evolution may also apply to other drugs, and knowledge of the rates and mechanisms could be used to design improved diagnostics and by tracking the evolution of infectious strains, to inform the optimization of therapies.
Keywords: tuberculosis; Salmonella; genomics; genetics; combination therapy
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Hughes, D.; Brandis, G. Rifampicin Resistance: Fitness Costs and the Significance of Compensatory Evolution. Antibiotics 2013, 2, 206-216.
Hughes D, Brandis G. Rifampicin Resistance: Fitness Costs and the Significance of Compensatory Evolution. Antibiotics. 2013; 2(2):206-216.
Hughes, Diarmaid; Brandis, Gerrit. 2013. "Rifampicin Resistance: Fitness Costs and the Significance of Compensatory Evolution." Antibiotics 2, no. 2: 206-216.