Cited by 627Tuberculosis Research and EpidemiologyEvolution and Genetic DynamicsInfectious Diseases and Tuberculosis

The Competitive Cost of Antibiotic Resistance in Mycobacterium tuberculosis

Gagneux, Sebastien, Long, Clara Davis, Small, Peter M., Van, Tran, Schoolnik, Gary K., Bohannan, Brendan J. M.·2006·Science

Abstract

Mathematical models predict that the future of the multidrug-resistant tuberculosis epidemic will depend on the fitness cost of drug resistance. We show that in laboratory-derived mutants of Mycobacterium tuberculosis, rifampin resistance is universally associated with a competitive fitness cost and that this cost is determined by the specific resistance mutation and strain genetic background. In contrast, we demonstrate that prolonged patient treatment can result in multidrug-resistant strains with no fitness defect and that strains with low- or no-cost resistance mutations are also the most frequent among clinical isolates.

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Crossref · 10.1126/science.1124410

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  • Compensatory mutations may subsequently arise to offset the major fitness cost of mutations conferring drug resistance.

    “suggesting that compensatory mutations may subsequently arise to offset the major fitness cost of mutations conferring drug”

    From The evolution of drug resistance in clinical isolates of Candida albicans. (2015) · cites this paper as Gagneux et al., 2006

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Authors
Gagneux, S., Long, C. D., Small, P. M., Van, T., Schoolnik, G. K., & Bohannan, B. J. M.
Affiliations
  • Division of Infectious Diseases and Geographic Medicine, Stanford University, Stanford, CA 94305, USA.
  • Gates Foundation (US)
Corresponding author
Long, Clara Davis
Venue
Science
Published
2006-06-30
Volume
312
Issue
5782
Pages
1944-1946
ISSN
  • 0036-8075 (ISSN-L)
  • 1095-9203
OpenAlex
W2090640084
Cited by
627
References
28
Citations by year
2026: 16 · 2025: 22 · 2024: 27 · 2023: 19 · 2022: 26 · 2021: 26 · 2020: 29 · 2019: 30 · 2018: 39 · 2017: 52 · 2016: 37 · 2015: 36 · 2014: 36 · 2013: 39 · 2012: 40
FWCI
18.38
Type
journal article
Language
en
Open access
closed
Locations
  • Science (publishedVersion)
  • PubMed (publishedVersion)
Funders
Wellcome Trust
Topics
  • Health Sciences › Medicine › Infectious Diseases › Tuberculosis Research and Epidemiology
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Evolution and Genetic Dynamics
  • Health Sciences › Medicine › Surgery › Infectious Diseases and Tuberculosis
Keywords
Mycobacterium tuberculosis, multidrug-resistant tuberculosis, rifampicin resistance, competitive fitness, resistance mutations, long-term treatment, clinical isolates
MeSH terms
Antibiotics, Antitubercular, Bacterial Proteins, Humans, Models, Biological, Mutation, Mycobacterium tuberculosis, Rifampin, DNA-Directed RNA Polymerases, Tuberculosis, Multidrug-Resistant, Amino Acid Substitution, Mutation, Missense, Drug Resistance, Multiple, Bacterial

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