Mycobacterium tuberculosis mutation rate estimates from different lineages predict substantial differences in the emergence of drug resistant tuberculosis

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Mycobacterium tuberculosis mutation rate estimates from different lineages predict substantial differences in the emergence of drug resistant tuberculosis

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Title: Mycobacterium tuberculosis mutation rate estimates from different lineages predict substantial differences in the emergence of drug resistant tuberculosis
Author: Ford, Christopher B.; Shah, Rupal R.; Maeda, Midori Kato; Gagneux, Sebastien; Murray, Megan B.; Cohen, Ted; Johnston, James C.; Gardy, Jennifer; Lipsitch, Marc; Fortune, Sarah M.

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Citation: Ford, Christopher B., Rupal R. Shah, Midori Kato Maeda, Sebastien Gagneux, Megan B. Murray, Ted Cohen, James C. Johnston, Jennifer Gardy, Marc Lipsitch, and Sarah M. Fortune. 2013. “Mycobacterium tuberculosis mutation rate estimates from different lineages predict substantial differences in the emergence of drug resistant tuberculosis.” Nature genetics 45 (7): 784-790. doi:10.1038/ng.2656. http://dx.doi.org/10.1038/ng.2656.
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Abstract: A critical question in tuberculosis control is why some strains of Mycobacterium tuberculosis are preferentially associated with multiple drug resistances. We demonstrate that M. tuberculosis strains from Lineage 2 (East Asian lineage and Beijing sublineage) acquire drug resistances in vitro more rapidly than M. tuberculosis strains from Lineage 4 (Euro-American lineage) and that this higher rate can be attributed to a higher mutation rate. Moreover, the in vitro mutation rate correlates well with the bacterial mutation rate in humans as determined by whole genome sequencing of clinical isolates. Finally, using a stochastic mathematical model, we demonstrate that the observed differences in mutation rate predict a substantially higher probability that patients infected with a drug susceptible Lineage 2 strain will harbor multidrug resistant bacteria at the time of diagnosis. These data suggest that interventions to prevent the emergence of drug resistant tuberculosis should target bacterial as well as treatment-related risk factors.
Published Version: doi:10.1038/ng.2656
Other Sources: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3777616/pdf/
Terms of Use: This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAA
Citable link to this page: http://nrs.harvard.edu/urn-3:HUL.InstRepos:11879508
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