2006/06/30 by Sébastien Gagneux, Clara Davis Long, Peter M. Small +3 · 1 citation
Medicine · Biochemistry, Genetics and Molecular Biology · #Tuberculosis Research and Epidemiology #Evolution and Genetic Dynamics #Mycobacterium research and diagnosis
paper · doi:10.1126/science.1124410
openalex publication_date 2006/06/30 · openalex created_date 2016/06/24 · openalex updated_date 2026/07/23
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.