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A microbiological examination by skin scab of a leprosy patient in Thailand.

Leprosy, a disfiguring scourge in Biblical times, still exists in the 21st century, despite the availability of many effective modern treatments. The some 200,000 cases counted by the World Health Organization show a growing number of stubborn bacteria developing new drug resistance.

Some Mycobacterium leprae germ varieties have developed an all-or-nothing game of biological chance to stake out their survival, according to a new study in the journal Nature Communications.

The eight key strains have a large number of random mutations in their DNA – and also have a compromised gene for DNA repair.

“It’s fascinating survival strategy against antibiotics,” said Andrej Benjak, lead author, of the École Polytechnique Fédérale de Lausanne, in a statement released by the Swiss school. “Disrupting DNA repair will result in a storm of random mutations, increasing the chance that the right gene mutates at the right spot and leads to drug resistance. But random mutations can be deadly, so it’s like a desperate, genetic Russian roulette for the bacterium.”

The international team, which included contributors from institutes from South America, Asia, Africa, and elsewhere, isolated and scrutinized the entire genomes from 154 samples of leprosy from 25 countries.

They extracted bacterial samples from skin biopsies of leprosy sufferers. They then used a customized protocol to extract the DNA, then enrich it onto Agilent SureSelect Capture Arrays which contain about 1 million DNA probes spanning the entire genome.

That step was then followed by elution and polymerase chain reaction amplification. The sequencing was performed on Illumina instruments.

Through the extra steps, they increase the bacterial DNA – and then reduced the patient’s DNA, they report.

The eight strains were found as the most potentially dangerous and drug-resistant strains.

Their reconstruction of the history of the dreaded disease indicates it originated in Eurasia, and the modern version appeared during the Iron Age. (The earliest written record is 600 B.C., according to the paper).

Currently, most leprosy is curable, especially through a multi-drug therapy option developed in the 1980s that includes rifampicin, dapsone, clofazimine, as well as second-line drugs including ofloxacin, minocycline, and clarithromycin.

But the newest drug-resistant strains have appeared to adapt to survive this therapy. The new work, the Swiss scientists say, could potentially mean the end of the disease’s spread.

“This is an important finding,” said Stewart Cole, the head of the laboratory at EPFL’s Global Health Institute. “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.”

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