TB genomes reveal secrets of pathogen`s success

Washington: Scientists, after analysing dozens of tuberculosis genomes gathered from around the world, are getting a lot more detailed image of why the pathogen is so prevalent and how it evolves to resist countermeasures.

A team led by University of Wisconsin-Madison researcher Caitlin Pepperell describes a bacterium that marches in lockstep with human population growth and history, evolving to take advantage of the most crowded and wretched human conditions.

Senior author Marcus Feldman of Stanford, said that TB experienced a 25-fold expansion worldwide in the 17th century, a time when human populations underwent explosive growth and European exploration of Africa, the Americas, Asia and Oceania was at its peak.

Pepperell said that the timing is coincident with expansion, urbanization and colonial migrations of global human populations, asserting that these findings suggest that much of the current TB pandemic has its origins in historical events of the last three centuries.

The analysis conducted by Pepperell and her colleagues focused on the role of natural selection, looking at patterns of genetic diversity among 63 TB and related pathogenic mycobacterial genomes gathered from around the globe.

The study shows a highly constrained bacterial genome, with most deleterious mutations quickly discarded. This was especially true for genes essential for causing disease, protein translation and the trafficking and metabolism of inorganic ions, which help control the interaction between the TB pathogen and its human host.

The bacterium`s "defense" genes, on the other hand, showed a high degree of tolerance for beneficial mutations, which may play a role in evolution of drug resistance and evasion of the human immune system.

Pepperell observed that evolutionary theory predicts that Mycobacterium tuberculosis populations should be vulnerable to extinction. Yet it is obviously highly prevalent, as it may have some incredibly clever strategies and tricks to hang on.

The study has been published in the journal Public Library of Science (PLoS) Pathogens.