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dc.contributor.authorFord, Christopher B.en_US
dc.contributor.authorShah, Rupal R.en_US
dc.contributor.authorMaeda, Midori Katoen_US
dc.contributor.authorGagneux, Sebastienen_US
dc.contributor.authorMurray, Megan B.en_US
dc.contributor.authorCohen, Teden_US
dc.contributor.authorJohnston, James C.en_US
dc.contributor.authorGardy, Jenniferen_US
dc.contributor.authorLipsitch, Marcen_US
dc.contributor.authorFortune, Sarah M.en_US
dc.date.accessioned2014-03-11T13:25:29Z
dc.date.issued2013en_US
dc.identifier.citationFord, 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.en
dc.identifier.issn1061-4036en
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:11879508
dc.description.abstractA 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.en
dc.language.isoen_USen
dc.relation.isversionofdoi:10.1038/ng.2656en
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC3777616/pdf/en
dash.licenseLAAen_US
dc.titleMycobacterium tuberculosis mutation rate estimates from different lineages predict substantial differences in the emergence of drug resistant tuberculosisen
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden
dc.relation.journalNature geneticsen
dash.depositing.authorFord, Christopher B.en_US
dc.date.available2014-03-11T13:25:29Z
dc.identifier.doi10.1038/ng.2656*
dash.contributor.affiliatedFord, Christopher Burton
dash.contributor.affiliatedMurray, Megan
dash.contributor.affiliatedFortune, Sarah
dash.contributor.affiliatedLipsitch, Marc


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