Genes associated with antibiotic resistance to leprosy have been isolated, sequenced and analyzed by an international team of scientists led by Stewart Cole's lab at EPFL's Global Health Institute. New genes that might point to previously unknown mechanisms of drug resistance have also been identified.
Leprosy is a communicable disease which is caused by the bacterium called Mycobacterium leprae
. The disease spreads with unpleasant or haunting symptoms in which the peripheral nerves, skin, eyes and the upper respiratory tract are very badly affected. Although the disease can be treated and cured by using multiple drug therapy, new cases of leprosy are recorded in various developing countries. It is estimated that more than 200,000 new cases are reported each year along with the emerging of drug resistant strains of M.leprae.
‘Strains of Mycobacterium leprae were analyzed for its drug resistant activity in treating leprosy and to facilitate preventive measures to avoid disease transmission.’
To fight leprosy, scientists need to better understand the biology of M. leprae
, and specifically how it interacts with its host and resists antibiotics. However, studying the bacterium is difficult, as it cannot be grown in a lab.
"This is an important finding," says Stewart Cole. "The way clofazimine, one of the main leprosy drugs, works is completely unknown but now we have a new lead to investigate thanks to this analysis of multidrug-resistant M. leprae."
Isolating M. leprae DNA was a challenging task, as the amount of bacteria in skin biopsies is generally low and varies greatly between patients. And after extracting the DNA, the researchers had to separate the bacterial DNA from the patient's. They did this with two techniques, one that increased the bacterium's DNA and one that decreased the patient's DNA. Once the bacterium's DNA was isolated, the researchers were able to sequence it and compare it with that from other samples.
The scientists also found eight strains of M. leprae whose genomes harbored an incredibly large number of random mutations, accumulated over a period of a few years or perhaps decades. These eight strains are all resistant to multi-drug therapy, and were the only ones in the study in which a gene that is responsible for DNA repair is disrupted.
"It's a fascinating survival strategy against antibiotics," explains Andrej Benjak, the study's leading author. "Disrupting DNA repair will result in a storm of random mutations, increasing the chance that the right gene mutates at the right spot and lead to drug resistance. But random mutations can be deadly, so it's like a desperate, genetic Russian roulette for the bacterium."
The researchers also discovered that leprosy itself might have originated in the Far East. Several bacterial strains from East Asia belonged to the ancestral lineages of the leprosy bacilli. "People naturally assume that old human diseases originated in Africa, but for leprosy, the evidence points to Eurasia," says Charlotte Avanzi, one of the study's authors from Cole's lab.
Narrowing down the location of the origin will facilitate the reconstruction of the spread of the disease. "We need more samples from Central Asia and the Middle East, but these are hard to get due to current geopolitical issues," says Avanzi. "For Europe, where leprosy is eradicated, we have to rely on ancient human remains. But it's possible -- we have developed the tools, and now we are ready to sequence even more samples."