If you want to find one of the most successful human pathogens of all time, you have to look no farther than the often-dramatized infection of tuberculosis. Why it shows up in so many literary works isn’t that difficult to figure out. The predecessor to today’s modern printing presses was first invented in 1450, causing an explosion of books to be created, which just so happened to be right around the same time as TB’s own proliferation.
According to a recent study, TB experienced a 25-fold explosion of worldwide growth in the 16th century, a period of time when Europeans were busy killing off the rest of the world’s native cultures. The study also goes on to try to determine why TB is so successful. After all, it is only transmitted between humans, it cannot survive outside of a host, and it often kills the carrier.
The key, according to its genetic diversity and history, is always betting on human behavior.
“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,” said Caitlin Pepperell, a professor of medicine and medical microbiology at the University of Wisconsin, who helped author the paper along with senior researcher Marcus Feldman of Stanford.
By studying 63 worldwide strains of TB, the researchers found a highly conserved central group of genes that don’t change much. 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.
But since the key to surviving an ever-changing immune defense system is mutations, there must also be a group of genes ready to adapt at a moments notice. These genes, the study revealed, are the bacterium’s “defense” genes, which showed a high degree of tolerance for beneficial mutations.
The identification of these genes is the first step toward trying to find a better way to fight the two billion infections that happen every year worldwide. While the “defense” genes may change up their configurations often, the more static genes offer a better place to target TB. Because they can’t change while maintaining the bacterium’s stability, any medicine that can target them is more likely to remain effective throughout different mutations and strains.
The study, “The Role of Selection in Shaping Diversity of Natural M. tuberculosis Populations,” was published by Pepperell and Feldman, along with Amanda Casto, Julie Granka and Omar Cornejo of Stanford; Andrew Kitchen of the University of Iowa; Eddie Holmes of the University of Sydney; and Bruce Birren and James Galagan of the Broad Institute.