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Local adaption of tuberculosis, not human migration, spread TB resistance mutations

Global expansion of Mycobacterium tuberculosis lineage four shaped by colonial migration and local adaptation

American Association for the Advancement of Science


IMAGE: Sampling overview and phylogeography of the global L4 dataset. view more 

Credit: Brynildsrud et al., Sci. Adv. 2018; 4 : eaat5869

Migration from Europe during the colonial period drove the spread of the dominant strain of tuberculosis seen today, lineage 4, a new study reports. Drug resistance to this infectious disease evolved independently in various regions multiple times, the study also suggests, with little international dissemination after independent disease evolution. These results have implications for tuberculosis' management and treatment, suggesting that efforts to contain this disease at the level of individual countries could be successful. In humans, tuberculosis (TB) is a disease caused by the bacterium, Mycobacterium tuberculosis (M.tb), which mainly affects the lungs. There are seven known M.tb lineages, or strains of this disease, and lineage 4 (L4) is the most widely spread around the world. The origin, spread and antimicrobial resistance qualities of L4, however, are not well-characterized. Ola B. Brynildsrud and colleagues analyzed 1,669 L4 genomes (more than 600 of which had not previously been published) from 15 countries, including those in Europe, Africa and the Americas. They discovered that L4's most recent common ancestor existed around 1096 CE and most likely originated in Europe (in the loose sense, potentially including in regions of west Asia and North Africa as well). Human migration from Europe during the colonial period was the main driver of L4 dispersion, the authors say, with the first wave towards Southeast Asia beginning around the 13th century, and the next wave directed towards Africa starting in the 15th century. This was followed by a wave to the Americas brought by European colonists soon after their arrival in 1492. Further analysis of specific genes within the strains revealed two intriguing features of this disease. Firstly, the lactate dehydrogenase gene lldD2, which is important for M.tb replication within host cells, has undergone parallel evolution at different sites around the world, starting long before the current age of antibiotics. Secondly, classical antibiotic resistance mutations appear to have arisen recently at multiple locations but show almost no large-scale geographical movement. In contrast to common belief, this suggests that parallel local adaptation, rather than human migration, is a major factor behind the spread of resistance mutations.


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