Researchers have just compared reconstructed genomes of the medieval strains of Mycobacterium leprae DNA – the pathogen responsible for leprosy – to modern day strains.
Leprosy, a chronic, contagious disease, is caused by a bacterium which affects mainly the skin and nerves. It was once an epidemic in Europe during the Middle Ages and wreaked absolute mayhem in the continent. Those suffering from the condition were shunned by society – even made to wear bells as a warning for others around them.
However, towards the end of the 16th century the prevalence abruptly declined. Some experts believed that it suddenly stopped affecting people because of it evolved into something less harmful.
However, new research reveals that lesprosy became less prevalent because of improved social conditions.
The researchers, led by Verena Schuenemann from the University of Tübingen in Tübingen, Germany, analyzed skeletal remains of five lepers who lived between the 10th and 14th centuries and managed to obtain almost complete genomes of M. leprae.
The team compared those genomes to ones that were sequenced from modern day strains of M. leprae, they found that the genome of the bacterium hasn’t changed much over the past millennium.
The report was published in the June 14 issue of Science.
Even with the development of effective drugs, every year leprosy affects over 225,000 people around the world.
Around 150 cases are diagnosed each year, with 3,000 people in the U.S. currently being treated for leprosy, said James Krahenbuhl, Ph.D., director of the Health Resources Service Administration’s National Hansen’s Disease Program (NHDP).
Using DNA capture techniques and high-throughput sequencing, the investigators managed to achieve remarkable coverage of the ancient M. leprae DNA. They obtained the contemporary M. leprae genomes by using recent biopsies from modern day leprosy patients.
Study coauthor Pushpendra Singh said: “We were able to reconstruct the genome without using any contemporary strains as a basis.”
Frontal view of the skull of one of the skeletal remains
Credit: Ben Krause-Kyora
The researchers found that the bacterium’s DNA degrades more slowly than human DNA because of unique protective acids in its thick cell walls.
Johannes Krause, a co-author of the Science paper, said:
“Since the M. leprae DNA degrades slower than human and probably other vertebrate DNA, it should be possible to extract and sequence M. leprae DNA from environments and time periods in which we would not usually find DNA preserved, like the tropics or early, prehistoric time periods. So potentially we could study samples from the time of the disease’s origin.”
The analysis reveals that the genome hasn’t mutated that much over the past 1,000 years. The team only identified 800 mutations. Schuenemann says that the modern day pathogen in the Americas most likely came from Europe.
The decline of leprosy in Europe is most likely due to cleaner living conditions, considering that the genes controlling the bacterium’s virulence haven’t changed over the centuries. It is also possible that other diseases like tuberculosis and the plague could have eclipsed it.
Krause said: “We’ve shown that the mutation rate of leprosy is rather low and that it has not changed much over time. Therefore, it is less likely to rapidly become antibiotic-resistant. At the same time, constant treatment with antibiotics might still change the genetic makeup of the strains.”
He added:
“Two of the [modern] strains show antibiotic-resistant mutations to the drug Dapsone. So, when doctors detect this strain in the future, they will already know that the patient should not be treated with Dapsone.
The next step will be to go back further in time to understand the adaptation of M. leprae throughout time and to learn about target genes that are essential to the bacterium, which may be targeted by drugs.”
The high quality of their genome sequences could allow them to even trace the prehistoric origins of the bacterium.
Only in the 1980s did an effective cure for leprosy become available – multidrug therapy, MDT – which led to over 15 million people being completely cured of the disease.
Written by Joseph Nordqvist