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

Oleh:

Ford, Christopher B ; Shah, Rupal R ; Maeda, Midori Kato ; Gagneux, Sebastien ; Murray, Megan B

Jenis: Article from Journal - ilmiah internasional
Dalam koleksi: Nature Genetics vol. 45 no. 07 (Jul. 2013), page 784–790 .

Ketersediaan

Perpustakaan FK Nomor Panggil: N12.K Non-tandon: 1 (dapat dipinjam: 0) Tandon: tidak ada

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Isi artikel

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.

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