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Science. 2006 Jun 30;312(5782):1944-6.

The competitive cost of antibiotic resistance in Mycobacterium tuberculosis.

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Division of Infectious Diseases and Geographic Medicine, Stanford University, Stanford, CA 94305, USA.


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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