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Rifampicin Resistance: Fitness Costs and the Significance of Compensatory Evolution
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 proble...
Autores principales: | , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4790335/ https://www.ncbi.nlm.nih.gov/pubmed/27029299 http://dx.doi.org/10.3390/antibiotics2020206 |
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author | Hughes, Diarmaid Brandis, Gerrit |
author_facet | Hughes, Diarmaid Brandis, Gerrit |
author_sort | Hughes, Diarmaid |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-4790335 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-47903352016-03-24 Rifampicin Resistance: Fitness Costs and the Significance of Compensatory Evolution Hughes, Diarmaid Brandis, Gerrit Antibiotics (Basel) Review 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. MDPI 2013-04-03 /pmc/articles/PMC4790335/ /pubmed/27029299 http://dx.doi.org/10.3390/antibiotics2020206 Text en © 2013 by the authors; licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/3.0/). |
spellingShingle | Review Hughes, Diarmaid Brandis, Gerrit Rifampicin Resistance: Fitness Costs and the Significance of Compensatory Evolution |
title | Rifampicin Resistance: Fitness Costs and the Significance of Compensatory Evolution |
title_full | Rifampicin Resistance: Fitness Costs and the Significance of Compensatory Evolution |
title_fullStr | Rifampicin Resistance: Fitness Costs and the Significance of Compensatory Evolution |
title_full_unstemmed | Rifampicin Resistance: Fitness Costs and the Significance of Compensatory Evolution |
title_short | Rifampicin Resistance: Fitness Costs and the Significance of Compensatory Evolution |
title_sort | rifampicin resistance: fitness costs and the significance of compensatory evolution |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4790335/ https://www.ncbi.nlm.nih.gov/pubmed/27029299 http://dx.doi.org/10.3390/antibiotics2020206 |
work_keys_str_mv | AT hughesdiarmaid rifampicinresistancefitnesscostsandthesignificanceofcompensatoryevolution AT brandisgerrit rifampicinresistancefitnesscostsandthesignificanceofcompensatoryevolution |