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Compensatory evolution drives multidrug-resistant tuberculosis in Central Asia

Merker, Matthias and Barbier, Maxime and Cox, Helen and Rasigade, Jean-Philippe and Feuerriegel, Silke and Kohl, Thomas Andreas and Diel, Roland and Borrell, Sonia and Gagneux, Sebastien and Nikolayevskyy, Vladyslav and Andres, Sönke and Nübel, Ulrich and Supply, Philip and Wirth, Thierry and Niemann, Stefan. (2018) Compensatory evolution drives multidrug-resistant tuberculosis in Central Asia. eLife, 7. e38200.

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Official URL: https://edoc.unibas.ch/66702/

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Abstract

Bacterial factors favoring the unprecedented multidrug-resistant tuberculosis (MDR-TB) epidemic in the former Soviet Union remain unclear. We utilized whole genome sequencing and Bayesian statistics to analyze the evolutionary history, temporal emergence of resistance and transmission networks of MDR; Mycobacterium tuberculosis; complex isolates from Karakalpakstan, Uzbekistan (2001-2006). One clade (termed Central Asian outbreak, CAO) dating back to 1974 (95% HPD 1969-1982) subsequently acquired resistance mediating mutations to eight anti-TB drugs. Introduction of standardized WHO-endorsed directly observed treatment, short-course in Karakalpakstan in 1998 likely selected for CAO-strains, comprising 75% of sampled MDR-TB isolates in 2005/2006. CAO-isolates were also identified in a published cohort from Russia (2008-2010). Similarly, the presence of mutations supposed to compensate bacterial fitness deficits was associated with transmission success and higher drug resistance rates. The genetic make-up of these MDR-strains threatens the success of both empirical and standardized MDR-TB therapies, including the newly WHO-endorsed short MDR-TB regimen in Uzbekistan.
Faculties and Departments:09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH)
09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH) > Department of Medical Parasitology and Infection Biology (MPI) > Tuberculosis Research (Gagneux)
UniBasel Contributors:Borrell Farnov, Sonia and Gagneux, Sebastien
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:eLife Sciences Publications
ISSN:2050-084X
Note:Publication type according to Uni Basel Research Database: Journal article
Language:English
Identification Number:
Last Modified:22 Nov 2018 13:02
Deposited On:22 Nov 2018 13:02

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