1. The competitive cost of antibiotic resistance in Mycobacterium tuberculosis.
- Author
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Gagneux S, Long CD, Small PM, Van T, Schoolnik GK, and Bohannan BJ
- Subjects
- Amino Acid Substitution, Antibiotics, Antitubercular therapeutic use, Bacterial Proteins genetics, DNA-Directed RNA Polymerases genetics, Humans, Models, Biological, Mutation, Mutation, Missense, Mycobacterium tuberculosis genetics, Rifampin therapeutic use, Tuberculosis, Multidrug-Resistant drug therapy, Antibiotics, Antitubercular pharmacology, Drug Resistance, Multiple, Bacterial, Mycobacterium tuberculosis drug effects, Mycobacterium tuberculosis growth & development, Rifampin pharmacology, Tuberculosis, Multidrug-Resistant microbiology
- 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.
- Published
- 2006
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