The Competitive Cost of Antibiotic Resistance in Mycobacterium tuberculosis

American Association for the Advancement of Science (AAAS) - Tập 312 Số 5782 - Trang 1944-1946 - 2006
Sébastien Gagneux1,2,3,4,5, Clara Davis Long1,2,3,4,5, Peter M. Small1,2,3,4,5, Trần Thị Thanh Vân1,2,3,4,5, Gary K. Schoolnik1,2,3,4,5, Brendan J. M. Bohannan1,2,3,4,5
1Bill and Melinda Gates Foundation, Seattle, WA 98102, USA.
2Department of Biological Sciences, Stanford University, Stanford, CA 94305 USA
3Department of Microbiology and Immunology, Stanford University, Stanford, CA 94305, USA
4Division of Infectious Diseases and Geographic Medicine, Stanford University, Stanford, CA 94305, USA
5Institute for Systems Biology, Seattle, WA 98103 USA

Tóm tắt

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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Tài liệu tham khảo

10.1126/science.293.5536.1786

T. M. File Jr., Chest115, 3S (1999).

D. I. Andersson, B. R. Levin, Curr. Opin. Microbiol.2, 489 (1999).

M. G. Reynolds, Genetics156, 1471 (2000).

S. Maisnier-Patin, D. I. Andersson, Res. Microbiol.155, 360 (2004).

F. M. Cohan, E. C. King, P. Zawadzki, Evol. Int. J. Org. Evol.48, 81 (1994).

B. Bjorkholm et al., Proc. Natl. Acad. Sci. U.S.A.98, 14607 (2001).

S. J. Schrag, V. Perrot, Nature381, 120 (1996).

E. C. Böttger, B. Springer, M. Pletschette, P. Sander, Nat. Med.4, 1343 (1998).

T. A. Wichelhaus et al., Antimicrob. Agents Chemother.46, 3381 (2002).

P. Sander et al., Antimicrob. Agents Chemother.46, 1204 (2002).

O. J. Billington, T. D. McHugh, S. H. Gillespie, Antimicrob. Agents Chemother.43, 1866 (1999).

World Health Organization Anti-Tuberculosis Drug Resistance in the World—Third Global Report G. T. C. Program Ed. (World Health Organization Geneva 2004).

J. S. Mukherjee et al., Lancet363, 474 (2004).

C. Dye, M. A. Espinal, Proc. R. Soc. London Ser. B268, 45 (2001).

S. M. Blower, T. Chou, Nat. Med.10, 1111 (2004).

T. Cohen, M. Murray, Nat. Med.10, 1117 (2004).

10.1126/science.1063814

S. Ramaswamy, J. M. Musser, Tuber. Lung Dis.79, 3 (1998).

D. H. Mariam, Y. Mengistu, S. E. Hoffner, D. I. Andersson, Antimicrob. Agents Chemother.48, 1289 (2004).

R. S. Lenski, M. R. Rose, S. C. Simpson, S. C. Tadler, Am. Nat.138, 1315 (1991).

L. Baker, T. Brown, M. C. Maiden, F. Drobniewski, Emerg. Infect. Dis.10, 1568 (2004).

10.1128/JB.184.19.5479-5490.2002

S. Gagneux et al., Proc. Natl. Acad. Sci. U.S.A.103, 2869 (2006).

A. G. Tsolaki et al., J. Clin. Microbiol.43, 3185 (2005).

P. F. Barnes, M. D. Cave, N. Engl. J. Med.349, 1149 (2003).

F. A. Post et al., J. Infect. Dis.190, 99 (2004).

10.1093/jac/dki069

We thank K. Kremer and A. Ponce de Leon for providing clinical strains. This research was supported by the NIH and the Wellcome Trust. S.G. was supported by the Swiss National Science Foundation and the Novartis Foundation.

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American Association for the Advancement of Science (AAAS)

Tập 312 Số 5782

1944-1946

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