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Science 30 June 2006:
Vol. 312. no. 5782, pp. 1944 - 1946
DOI: 10.1126/science.1124410
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Reports

The Competitive Cost of Antibiotic Resistance in Mycobacterium tuberculosis

Sebastien Gagneux,1,4*{dagger} Clara Davis Long,2* Peter M. Small,4,5 Tran Van,1 Gary K. Schoolnik,1,3 Brendan J. M. Bohannan2

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.

1 Division of Infectious Diseases and Geographic Medicine, Stanford University, Stanford, CA 94305, USA.
2 Department of Biological Sciences, Stanford University, Stanford, CA 94305, USA.
3 Department of Microbiology and Immunology, Stanford University, Stanford, CA 94305, USA.
4 Institute for Systems Biology, Seattle, WA 98103, USA.
5 Bill and Melinda Gates Foundation, Seattle, WA 98102, USA.

* These authors contributed equally to this work.

{dagger} To whom correspondence should be addressed. E-mail: sgagneux{at}systemsbiology.org

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