Natural Antibiotic Kills Tuberculosis Bacterium

Natural Antibiotic Kills Tuberculosis Bacterium

Author: ChemistryViews

Ruben C. Hartkoorn, Global Health Institute, Switzerland, and colleagues have 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 bacteriua that no longer respond to treatment with the front-line drug isoniazid.

The researchers selected and isolated mutants of the tuberculosis bacterium Mycobacterium tuberculosis that are resistant to pyridomycin. By sequencing their genome a single gene named inhA was found to be responsible for resistance to pyridomycin.
The gene inhA is needed to produce the InhA protein, which is already known as a target for the tuberculosis drug isoniazid. Pyridomycin can bind 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. It is these differences that give pyridomycin the ability to overcome drug-resistant strains of mycobacteria.

In live bacteria treatment with pyridomycin leads to the depletion of mycolic acids, fatty acids that are an essential component of the bacterial cell wall.

EMBO Molecular Medicine
, one of the highest cited journals in the biomedical sciences, is now a fully Open Access journal.

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