edoc

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

Ford, Christopher B. and Shah, Rupal R. and Maeda, Midori Kato and Gagneux, Sebastien and Murray, Megan B. and Cohen, Ted and Johnston, James C. and Gardy, Jennifer and Lipsitch, Marc and Fortune, Sarah M.. (2013) Mycobacterium tuberculosis mutation rate estimates from different lineages predict substantial differences in the emergence of drug-resistant tuberculosis. Nature genetics, Vol. 45, H. 7. S. 784-790.

Full text not available from this repository.

Official URL: http://edoc.unibas.ch/dok/A6164958

Downloads: Statistics Overview

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.
Faculties and Departments:09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH) > Department of Medical Parasitology and Infection Biology > Tuberculosis Research (Gagneux)
09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH)
UniBasel Contributors:Gagneux, Sebastien
Item Type:Article, refereed
Bibsysno:Link to catalogue
Publisher:Nature Publ
ISSN:1061-4036
Note:Publication type according to Uni Basel Research Database: Journal article
Related URLs:
Identification Number:
Last Modified:27 Feb 2014 15:46
Deposited On:27 Feb 2014 15:46

Repository Staff Only: item control page