NEW YORK (GenomeWeb) – As Europeans colonized different regions of the world, they also spread a common tuberculosis lineage, according to a new study.
There are seven lineages of Mycobacterium tuberculosis, the bacterium that causes TB, two of which — lineages 2 and 4 — are distributed globally. An international team of researchers analyzed nearly 1,700 L4 M.tb genomes to untangle the history of its spread and the emergence of antibiotic resistance in the lineage. As they reported today in Science Advances, the researchers found that L4 originated in Europe and spread from there to Southeast Asia, Africa, and the Americas, mirroring European colonial history. Antibiotic resistance, however, has emerged locally within the lineage, and has not yet spread between regions.
"Successfully mapping past migration in this level of detail is a key first step to understanding the spread of disease in order to predict what might happen next, which is the ultimate goal," senior author and Norwegian Institute of Public Health researcher Vegard Eldholm said in a statement.
The researchers analyzed 1,669 clinical M.tb isolates from 15 different countries. They noted that sub-lineages of L4 were widely distributed, but that some were more common in particular areas. L4.5, for instance, was only found in Southeast Asia.
Using discrete trait analyses and Bayesian-structured coalescent approximation, the investigators assessed the phylogeographic history of L4. They found that the most recent common ancestor of L4 existed around 1096 AD within Europe. From there, L4 spread as Europeans colonized other parts of the world. The first wave took place at the beginning of the 13th century to Southeast Asia, the researchers said. The next waves flowed to Africa, particularly to what is now the Republic of Congo in the 15th century, and then to South Africa, Uganda, and Malawi. Then three waves of migration occurred from Europe to the Americas, suggesting that Europeans brought TB to South America shortly after their arrival in the late 1400s.
Over time, 733 mutations emerged more than once within L4, including ones affecting the lactate dehydrogenase gene lldD2. This gene has been thought to be important for enabling M.tb replication within human macrophages as it allows the bacterium to use lactate as a carbon source. Strains with lldD2 promoter mutations are more highly transmissible, the researchers found. They also noted that these mutations appeared before the use of antibiotics, suggesting parallel evolution, likely in response to changes in host ecology.
In recent years, there has been a slight decline in global TB burden, but the emergence of drug-resistant strains has challenged those efforts, the researchers added. Their analysis showed that known resistance genes repeatedly cropped up, but did so locally — they did not find any instance of a resistant strain crossing country borders. This suggested to them that drug-resistant TB could still be confronted regionally.
"Our findings strongly suggest that at least for Lineage 4, antibiotic resistance is a local challenge present in multiple countries and regions, but with minimal spread between them. Therefore, countries that succeed in halting transmission of resistant strains within their territory should expect to see a massive decrease of drug resistant TB," Eldholm said.
However, he and his colleagues warned that drug-resistant strains of TB are still able to spread. "This is not to say that we should not be worried about the international spread of resistant strains, as these patterns might well change in the future, especially if the burden of antibiotic resistance keeps growing," he added.