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LAUSANNE – Ecole Polytechnique Federale de Lausanne (EPFL) researchers have opened the door to a new strategy to fight tuberculosis, the second leading cause of death from infectious disease after HIV. In a study published in EMBO Molecular Medicine on September 17th, takes a hard look at the natural product pyridomycin, first reported in the 1950s, and determines exactly how it kills Mycobacterium tuberculosis.
Pyridomycin inhibits a vital enzyme, much like the best frontline antibiotics, but in a sufficiently different way so it can combat even the most antibiotic-resistant strains that have recently afflicted Russia, South Africa and North America.
“We’ve rediscovered an old antibiotic that was never developed but may lead the way to treating both drug-sensitive and drug-resistant strains of TB. And above all, the strategy of revisiting antibiotics to find new leads looks like a successful one,” said EPFL professor Stewart Cole.
The rise and fall of TB treatment
Tuberculosis is not a disease of the past. Infections take 1.4 million lives every year, with the majority of those cases occurring in Asia and Africa. Drug-resistant strains of TB from places like India and the former Soviet Union are a global threat to public health, often brought to new countries by immigrant populations. More alarmingly, several strains have been discovered that are totally impervious to all currently available treatments. Once a resistant strain infects a human, there is little hope for survival.
Today’s antibiotic dilemma can be traced back to the 1950s, when a new synthetic compound called “isoniazid” proved to be extremely effective against the malady. Nevertheless, with the recent onset of isoniazid-resistant strains, proper treatment involves four drugs and can last up to two years. Isoniazid has lost its status as the TB wonder drug.
New drug target, new hope
“We have discovered what’s known in the pharmaceutical world as a new drug target, opening the door for the development of new drugs and therapies that attack the same mechanism,” explained Professor Cole.
Looking for a drug that will kill isoniazid-resistant strains led StewartCole on an investigative journey into the past. With a combination of scientific foresight and serendipity, Cole found pyridomycin, an antibiotic extracted from a soil microbe. It was discovered around the same time as isoniazid but was left by the wayside for 60 years.