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Researchers in Switzerland have
shown that pyridomycin, a natural antibiotic produced by the soil bacterium
Dactylosporangium fulvum, may lead to the development of a new antituberculosis
drug.
According to Stewart Cole, lead
author of the study, a member of the European Molecular Biology Organization
(EMBO), and a professor at the École Polytechnique Fédérale de Lausanne in
Switzerland, pyridomycin is a very selective killer of Mycobacterium
tuberculosis. It is also active against bacteria resistant to isoniazid, a
first-line drug for treating TB.
The researchers identified a protein
called InhA, as the target of the antibiotic. The gene InhA is necessary for
producing the InhA protein, which is also a target for the TB drug isoniazid.
Pyridomycin binds to a different site on the InhA enzyme than isoniazid. Using
live bacteria, the researchers showed that pyridomycin led to depletion of
mycolic acids. These are fatty acids that are an essential to the component of
the bacterial cell wall.
Cole noted that the finding that
pyridomycin kills the TB bacterium by inhibiting InhA, even in bacteria
resistant to the drug isoniazid, means that there is a possibility of developing
pyridomycin or a related agent as treatment for drug-resistant TB.
The study, “Towards a New
Tuberculosis Drug: Pyridomycin – Nature's Isoniazid,” was published ahead of
the print version of EMBO Molecular Medicine [17 September 2012; DOI:
0.1002/emmm.201201689].
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