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- Title
Mycobacterium tuberculosis mutation rate estimates from different lineages predict substantial differences in the emergence of drug-resistant tuberculosis.
- Authors
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
- Abstract
A key question in tuberculosis control is why some strains of M. tuberculosis are preferentially associated with resistance to multiple drugs. 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.
- Subjects
TUBERCULOSIS treatment; MYCOBACTERIUM tuberculosis; MULTIDRUG-resistant tuberculosis; BACTERIAL mutation; MATHEMATICAL models; TUBERCULOSIS risk factors; NUCLEOTIDE sequence
- Publication
Nature Genetics, 2013, Vol 45, Issue 7, p784
- ISSN
1061-4036
- Publication type
Article
- DOI
10.1038/ng.2656