Leprosy has just shed some of its mystery. For the first time ever, a DNA analysis of Mycobacterium lepromatosis — a recently discovered bacteria that can cause a severe form of leprosy — reveals that the organism separated from its more common counterpart, Mycobacterium leprae, about 14 million years ago. The finding, published today in Proceedings of the National Academy of Sciences, could lead to better diagnostic tests and a more accurate map of leprosy’s geographic distribution. But it’s also intriguing in its own right: it shows that despite having broken off into separate species long ago, two pathogens can continue to infect a host — humans — in very similar ways.
about 200,000 new infections each year
Leprosy is a rare and painful chronic infection that can lead to skin lesions, vision problems, and the loss of extremities. Doctors see about 200,000 new infections each year, in countries such as India, Mexico, Brazil, Indonesia, and the Philippines. The small number of cases may have contributed to our limited knowledge of the disease; until recently, researchers thought that a single organism — Mycobacterium leprae — was responsible for all those cases. But that changed eight years ago.
"There were some strong reactions from the leprosy community and disbelief," says Xiang-Yang Han, a microbiologist at The University of Texas who discovered that leprosy is caused by two bacterial species. "I discovered [Mycobacterium lepromatosis] in 2007, and published the results 2008." An analysis demonstrated that the organisms were very similar; the two species "are cousins," Han says. Unfortunately, without a full DNA sequence, it was hard to know exactly what linked the two species together — or how long ago they went their separate ways.
"very similar sets of genes despite having diverged around 14 million years ago."
By analyzing human tissue infected with the bacteria, researchers were able to extract bacterial DNA and compare the genomes of both species. The comparison helped them pinpoint the timing of their separation, which the researchers say happened about 14 million years ago. "The most surprising for us was the fact that the genomes of the two species had very similar sets of genes despite having diverged around 14 million years ago," says Andrej Benjak, a geneticist at the Swiss Federal Institute of Technology in Lausanne, and one of the co-authors of the study. About 10 percent of their DNA sequence is different, which means that "most of the genes present in one species are also present in the other."
Some changes did occur, however. Over 300,000 mutations differentiate the two species, Benjak says. These changes don't appear to have significantly altered the way the bacteria act on humans, however. This means that the two species probably evolved as "leprosy-causing agents" a long time ago, Benjak says. And after that, they didn’t deviate from their evolutionary path.
After that, they didn’t deviate from their evolutionary path
The study "is pretty much as good as it gets," says Han, who didn't take part in this study. Because the species can’t be cultivated in a lab — the pathogens can only grow on living host organisms — "we could only do a descriptive analysis of the genome sequence and deduce that M. leproamatosis has a similar biology as M. leprae," Benjak says. This is pretty standard; delving deeper into the physiological aspects of bacteria that can't survive on its own is very challenging, if not impossible, he says.
Still, having a genetic blueprint like this one is just the first step, Han says. "With this whole genome in hand we can develop more diagnostic tools." And having better diagnostics will could lead to a more accurate map of M. lepromatosis' geographic distribution. Right now, "it seems to be restricted to Mexico and probably the surrounding area, but it does not seem to be globally ubiquitous as M. leprae," Benjak says. But Han says that some cases have been observed Singapore as well.
In an interesting twist, Han admits that his own team of researchers has also just sequenced the genome of M. lepromatosis, the species he discovered. They hope to publish an announcement to that effect in the coming weeks. "It just took us a little longer," he says. "We will learn from them."