Armed conflict and population displacement as drivers of the evolution and dispersal of Mycobacterium tuberculosis
- Vegard Eldholma,1,
- John H.-O. Petterssona,
- Ola B. Brynildsruda,
- Andrew Kitchenb,
- Erik Michael Rasmussenc,
- Troels Lillebaekc,
- Janne O. Rønninga,
- Valeriu Crudud,
- Anne Torunn Mengshoela,
- Nadia Debecha,
- Kristian Alfsnesa,
- Jon Bohlina,
- Caitlin S. Pepperelle,f, and
- Francois Ballouxg
- aInfection Control and Environmental Health, Norwegian Institute of Public Health, 0456 Oslo, Norway;
- bDepartment of Anthropology, University of Iowa, Iowa City, IA 52242;
- cInternational Reference Laboratory of Mycobacteriology, Statens Serum Institute, DK-2300 Copenhagen, Denmark;
- dMicrobiology and Morphology Laboratory, Phthisiopneumology Institute, MD 2025 Chisinau, Moldova;
- eDivision of Infectious Disease, Department of Medicine, School of Medicine and Public Health, University of Wisconsin–Madison, Madison, WI 53706;
- fDepartment of Medical Microbiology and Immunology, School of Medicine and Public Health, University of Wisconsin–Madison, Madison, WI 53706;
- gUCL Genetics Institute, University College London, London WC1E 6BT, United Kingdom
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Edited by Richard E. Lenski, Michigan State University, East Lansing, MI, and approved October 20, 2016 (received for review July 12, 2016)
Significance
We used population genomic analyses to reconstruct the recent history and dispersal of a major clade of Mycobacterium tuberculosis in central Asia and beyond. Our results indicate that the fall of the Soviet Union and the ensuing collapse of public health systems led to a rise in M. tuberculosis drug resistance. We also show that armed conflict and population displacement is likely to have aided the export of this clade from central Asia to war-torn Afghanistan and beyond.
Abstract
The “Beijing” Mycobacterium tuberculosis (Mtb) lineage 2 (L2) is spreading globally and has been associated with accelerated disease progression and increased antibiotic resistance. Here we performed a phylodynamic reconstruction of one of the L2 sublineages, the central Asian clade (CAC), which has recently spread to western Europe. We find that recent historical events have contributed to the evolution and dispersal of the CAC. Our timing estimates indicate that the clade was likely introduced to Afghanistan during the 1979–1989 Soviet–Afghan war and spread further after population displacement in the wake of the American invasion in 2001. We also find that drug resistance mutations accumulated on a massive scale in Mtb isolates from former Soviet republics after the fall of the Soviet Union, a pattern that was not observed in CAC isolates from Afghanistan. Our results underscore the detrimental effects of political instability and population displacement on tuberculosis control and demonstrate the power of phylodynamic methods in exploring bacterial evolution in space and time.
Footnotes
- ↵1To whom correspondence should be addressed. Email: v.eldholm{at}gmail.com.
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Author contributions: V.E. designed research; V.E., J.O.R., N.D., K.A., C.S.P., and F.B. performed research; V.E., E.M.R., T.L., V.C., and A.T.M. contributed new reagents/analytic tools; V.E., J.H.-O.P., O.B.B., A.K., K.A., J.B., C.S.P., and F.B. analyzed data; and V.E., J.H.-O.P., O.B.B., A.K., J.B., C.S.P., and F.B. wrote the paper.
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The authors declare no conflict of interest.
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This article is a PNAS Direct Submission.
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Data deposition: The sequences have been deposited in the European Molecular Biology Laboratory database, www.ebi.ac.uk/embl/index.htm (accession nos. PRJEB12184, PRJEB9680, ERP006989, and ERP000192).
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This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.1073/pnas.1611283113/-/DCSupplemental.
Freely available online through the PNAS open access option.
