A natural product secreted by a soil bacterium shows promise as a new drug to treat tuberculosis report scientists in a new study published in EMBO Molecular Medicine. A team of scientists working in Switzerland has shown how pyridomycin, a natural antibiotic produced by the bacterium Dactylosporangium fulvum, works. This promising drug candidate is active against many of the drug-resistant types of the tuberculosis bacterium that no longer respond to treatment with the front-line drug isoniazid.
"Nature and evolution have equipped some bacteria with potent defense mechanisms to protect them against other bugs that share their habitat. Screening natural products generated by these organisms is therefore a powerful way to find possible new drugs to fight infectious diseases," said Stewart Cole, lead author of the study, EMBO Member and a professor at the -cole Polytechnique F-d-rale de Lausanne (EPFL), Switzerland. "Using this approach we have shown that nature's antibiotic pyridomycin is a very selective killer of Mycobacterium tuberculosis, the bacterium responsible for tuberculosis in humans. It is also active against mycobacteria that have developed resistance to front-line drug treatments such as isoniazid."
Tuberculosis causes up to two million deaths annually. There is a significant need for new drugs since the effectiveness of current antibiotics is compromised by the increasing prevalence of drug-resistant tuberculosis. The most effective drugs used to treat tuberculosis, for example isoniazid and rifampicin, are often no longer effective.
The researchers identified a protein, the enzyme NADH-dependent enoyl(acyl carrier protein) reductase or InhA, which is the principal target for the antibiotic. "By selecting and isolating M. tuberculosis mutants resistant to pyridomycin and sequencing their genome we have found that a single gene named inhA is responsible for resistance to this natural product," added Cole.