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New Study Finds That TB Bacteria May Adapt to Ecological Niches

A team of 75 researchers from 56 institutions have conducted a global study of tuberculosis strains, finding that some may have adapted to specific human populations.

Tuberculosis (TB) is one of the leading causes of death worldwide, and now, a research team studying Mycobacterium tuberculosis bacterial samples from around the world have found that while some strains are generalists found worldwide, others are specialists that only exist in certain ecological niches.

In 2015, TB caused illness in 10.4 million individuals and killed 1.8 million individuals worldwide, according to the World Health Organization (WHO). While patients from just six countries make up 60% of all TB cases, we know the scope to be global, with nearly one-quarter of the world’s population currently infected with latent TB. Recent studies have made important findings about how TB impacts certain communities, including the discovery that multidrug-resistant TB is more widespread in Western Africa than previously believed and research into why the epidemic has been so hard for health officials to eradicate.

The new study analyzing strains of TB bacteria from around the world was conducted with the cooperation of a team of 75 researchers from 56 institutions, and was recently published in the journal Nature Genetics. In their investigation, they conducted genetic analysis on TB bacteria isolated from several thousand patients in more than 100 countries. While there’s a global range of TB strains, Mycobacterium tuberculosis lineage 4 has the greatest worldwide distribution and causes most TB illnesses. Based on previous studies and their own observations, the research team knew that TB bacteria are phylogenetically diverse, with seven phylogenetic lineages adapted to humans and two lineages adapted to various wild and domestic animal species. Lineage 2 strains of Mycobacterium tuberculosis are associated with higher drug resistance, while lineages 5, 6, and 7 are mostly found in West and East Africa.

What the researchers did not know is why lineage 4 bacteria showing enhanced virulence have been so successful throughout all the human-inhabited continents, but that the lineage’s success is a sign of genetic and phenotypic diversity. By studying the diversity of lineage 4 samples from around the world, the team aimed to better understand the success of these pathogens. Through genetic sequencing, the researchers found that lineage 4 comprises at least 10 sublineages that differ based on geographic distribution. Much like how ecologists differentiate organisms based on their ecological niches, the research team, for the first time, was able to apply the concept of generalists and specialists to a pathogen, finding that the Mycobacterium tuberculosis complex (MTBC) pathogen can be divided into generalists with worldwide distribution and specialists that only inhabit localized geographic areas.

Based on their findings, the team believes specialists would not be as successful if brought into new niches. “African specialist TB bacteria have likely been transported to the new world during the slave trade,” co-lead author Sebastien Gagneux, PhD, explained to Contagion. “But today, these strains are essentially absent from the Americas, suggesting that either this new niche was not appropriate or, more likely, they were facing competition from generalist TB bacteria introduced by Europeans who also migrated to the new world by the millions in the nineteenth century.”

The team studied the distribution patterns of TB sublineage prevalence to understand the adaptations of TB pathogens to human hosts. “Humans differ in their susceptibility to tuberculosis, and human genetic diversity may thus determine the width of the ecological niche accessible to differ­ent MTBC genotypes,” the authors wrote. “The geographical restriction of particular MTBC genotypes might reflect local adaptation of these pathogen variants to the corresponding human host populations. The geographical restriction of particular MTBC genotypes might reflect local adaptation of these pathogen variants to the corresponding human host populations.”

In their findings, the researchers also found that generalists exhibit more diversity in their antigens than specialists. “Generalists are thus able to react more specifically to the immune system of different human populations,” said co-lead author Stefan Niemann, in a recent press release from DZIF, the German Center for Infection Research. He explains that by adapting their molecular strategy these generalists have been more successful in spreading globally.

While their study sheds light on the epidemiology of successful TB strains, the authors noted that the greater antigenic adaptability of widespread generalists poses a challenge for researchers working on designing a TB vaccine, and that their findings explain why such a vaccine may continue to be elusive.

“There is currently a lot of effort put into developing new TB vaccines,” said Dr. Gagneux. “The field has not gotten very far despite the millions of dollars that have been invested. Our work shows that TB is different than many diseases. The fact that these different TB bacterial variants affect preferentially different human population suggests that developing a universally active vaccine against all the different TB bacteria might be particularly difficult.”