Plant-Based Drug To Fight Resistant TB

Researchers have identified plant-based compounds that could possibly be used to treat drug-resistant tuberculosis.

AsianScientist (Dec. 24, 2015) – by Claudia Caruana – Scientists from India and the US say they have discovered a group of compounds that can kill Mycobacterium tuberculosis, the bacterium responsible for causing tuberculosis (TB), by disabling a major defense mechanism it uses to survive in the human body.

The study, supported by the National Institutes of Health, India’s ministry of science and technology and the Wellcome Trust-Department of Biotechnology alliance was published in ACS Chemical Biology.

“These compounds show tremendous promise as lead scaffolds for the development of new, anti-TB treatments. Specifically, these compounds inhibit the function of a critical enzyme responsible for survival of M. tuberculosis,” said Amit Singh at the department of microbiology and cell biology, center for infectious disease and research at the Indian Institute of Science, Bangalore.

Singh said the new compounds belong to the ellipticine plant alkaloid family, which also is active in targeting cancerous cells.

“The active compounds have exerted a very high activity against drug-resistant M. tuberculosis strains isolated from patients of Indian origin,” he explained.

Alkaloid-containing plants have been used from ancient times to treat diseases or as intoxicants.

India has the highest burden of TB in the world with an estimated two million cases annually, with many individuals infected with the multi-drug resistant (MDR) and extensively drug-resistant (XDR) strains as well.

Some 95 percent of deaths from TB occur in developing countries in Asia and Africa. The six countries that stood out as having the largest numbers in 2014 were China, India, Indonesia, Nigeria, Pakistan and South Africa.

Kate Carroll, chemistry professor at the Scripps Research Institute and lead author of the study, stressed that individuals infected with dormant bacteria do not show any symptoms but may serve as a reservoir for M. tuberculosis.

“The problem is that this reservoir is gigantic with an estimated two billion people in the world carrying latent TB infection,” she said.

Carroll added that the new compounds have shown potent bactericidal activity against active as well as dormant form of drug-susceptible and MDR/XDR strains.

“Currently, we are testing their effectiveness in animal models of TB infection and once their pre-clinical and clinical effectiveness is confirmed, these compounds or their analogs can be potentially used in the treatment of MDR/XDR TB as well as persistent TB infection,” explained Carroll.

Carroll said the new compounds may be given alone, or more effectively, as a combination of multiple drugs. “These compounds can break a key bacterial defence and potentiate the action of other anti-TB drugs as well as kill persistent M. tuberculosis bacterium on their own,” she said.

Singh’s lab has also generated a series of compounds that were found to exert efficient killing of drug-resistant superbugs. He proposed to target mechanisms involved in resisting oxidative stress or elevating the levels of oxidative stress inside bacterial cells as strategies against TB infection.

The article can be found at: Palde et al. (2015) First-in-Class Inhibitors of Sulfur Metabolism with Bactericidal Activity against Non-Replicating M. tuberculosis.


Source: SciDev.Net; Photo: NIAID/Flickr/CC.
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