Natural Antibiotic Kills TB Bacterium
Researchers say pyridomycin is active against isoniazid-resistant bugs (Sept. 17)
A natural product secreted by a soil bacterium shows promise as a new drug to treat tuberculosis (TB), according to a September 17 announcement from the European Molecular Biology Organization (EMBO).
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 TB bacterium that no longer respond to treatment with the front-line drug isoniazid.
The team’s findings were reported in EMBO Molecular Medicine.
TB 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 TB. The drugs most commonly used to treat the disease, such as isoniazid and rifampicin, are often ineffective.
The researchers identified a protein — enzyme NADH-dependent enoyl(acyl carrier protein) reductase (InhA) — as the principal target for pyridomycin. By selecting and isolating Mycobacterium tuberculosis mutants resistant to pyridomycin and by sequencing their genome, the scientists found that a single gene, inhA, is responsible for pyridomycin resistance.
The gene inhA is needed to produce the InhA protein, which is a target for the TB drug isoniazid. Pyridomycin binds to the same pocket on the InhA enzyme as isoniazid but at a different site and in a way that involves a different sequence of molecular events. These differences give pyridomycin the ability to overcome drug-resistant strains of mycobacteria.
For more information, visit the EMBO Web site.