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New analysis of tuberculosis (TB) genomes gathered from around the world has revealed secrets of the pathogen's brilliance in adapting itself to prey on human poverty.
By any measure, TB is highly successful in its basic success criteria of survival and replication. The authors give estimates that TB infects one-third of the world's population. It has also firmly resisted all attempts at countermeasures.
Now, thanks to close analysis of dozens of TB genomes, a team of scientists led by Professor Caitlin Pepperell of UW-Madison's department of medical biology and immunology has been able to assemble a more detailed picture of how the TB bacterium uses ruthless natural selection to adapt and perfect itself.
In their paper published in the Pathogens section of the Public Library of Science (PLoS), the team describe a bacterium that has evolved and synchronized with human population growth and development, optimizing itself to exploit particularly crowded and impoverished human settlements.
"It's as though the bacterium places bets on human behavior," says Prof. Pepperell, formerly of Stanford University:
"It always bets that humans will go to war, send people to refugee camps, and gather in miserable places. Historically, that's been a winning bet on the bacterium's part."
The study, whose senior author is Marcus Feldman of Stanford, 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.
Their analysis reveals the degree to which the evolution of TB genome variations indicates a "purifying" selection process and close matching with patterns of human populations' geographic spread and phylogeny.
The study also suggests that tuberculosis bacteria "instantaneously" expanded at least 25-fold in the 1680s, near the peak of European exploration and colonization of Africa, the Americas, Asia and Oceania, and at a time when world population had begun to show exponential growth.
"The timing is coincident with expansion, urbanization and colonial migrations of global human populations," Prof. Pepperell explains. "These findings suggest that much of the current TB pandemic has its origins in historical events of the last three centuries."
TB can only survive and spread within humans - not in the wider environment. It particularly thrives in the crowded conditions of prisons, refugee camps and slums, and TB populations tend to be dominated by the bacteria "lucky" enough to land in those environments.
The study shows a highly constrained bacterial genome, with most deleterious mutations quickly discarded. The team said 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.
Prof. Pepperell notes:
"Evolutionary theory predicts that Mycobacterium tuberculosis populations should be vulnerable to extinction. Yet it is obviously highly prevalent. It must have some incredibly clever strategies and tricks to hang on."
As a result, the explosive spread of TB parallels the growth of human populations and takes every advantage of a world in which most people live in crowded and impoverished conditions.
Prof. Pepperell says the study should help other researchers home in on genes that may be good candidates for targeting with new drugs, and aid disease control strategies that accommodate or even co-opt the bacterium's evolution mechanisms to help speed its extinction.
Written by: Nick Valentine
Copyright: Medical News Today
Not to be reproduced without the permission of Medical News Today.
The role of selection in shaping diversity of natural M. tuberculosis populations Caitlin Pepperell, Amanda Casto, Andrew Kitchen and others, PLoS Pathog 9(8): e1003543. Open-access journal published online August 15th, 2013 (doi:10.1371/journal.ppat.1003543).
Visit our Tuberculosis category page for the latest news on this subject.
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Valentine, Nick. "How TB evolves to get the better of humans." Medical News Today. MediLexicon, Intl., 27 Aug. 2013. Web.
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