The bacterium responsible for leprosy evolves resistance to antibiotics by a crash-or-crash-through strategy involving large numbers of random mutations, scientists have found.
Sequencing the DNA of 154 strains of Mycobacterium leprae, the microbe responsible for the disease that infects about 200,000 people every year, researchers led by Stewart Cole from the Ecole Polytechnique Federale de Lausanne in Switzerland found eight varieties containing very high quantities of mutated genes.
The genes, the scientists report, had been accumulated over a period not longer than a few decades and possibly over just a few years. In all eight cases, the gene that governs the repair of the microbe’s own DNA had been disabled, and all were resistant to multiple forms of antibiotic.
“It’s a fascinating survival strategy against antibiotics,” explains co-author Andrej Benjak.
“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.”
Despite its long-recorded history of blighting humanity, surprisingly little is known about the make-up and mechanisms of M. leprae. How it interacts with its host and how it reacts to antibiotics are still mysteries.
In non-resistant strains it can be treated, and defeated, using a medication called clofazimine, but Cole characterises the way the drug works as “completely unknown”.
Even securing sufficient leprosy DNA to sequence proved challenging. Only very low amounts can be acquired through skin biopsies, with the total varying considerably between patients.
With each biopsy, separating M. leprae genetic material from that of its host was difficult. Cole’s team used two complementary techniques – the first promoting growth of the bacterial material, and the second suppressing human DNA.
Once isolated, the microbial DNA was sequenced and all 154 strains compared.
The researchers traced the oldest leprosy lineages to Asia, which came as a mild surprise because it had been assumed that the disease, like most ancient afflictions, originated in Africa.
The researchers say tracking down the origin of the disease more precisely will help them reconstruct its history and spread. To achieve that, however, they need more material.
“We need more samples from Central Asia and the Middle East, but these are hard to get due to current geopolitical issues,” says co-author Charlotte Avanzi.