Plant-based drug can fight resistant TB
- New compounds work by disabling a protective enzyme produced by TB bugs
- The compounds originate from the ellipticine plant-alkaloid family
- Both dormant and highly drug-resistant TB bugs can be dealt with
BANGALORE, December 20, 2015 - 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 defence mechanism it uses to survive in the human body.
Amit Singh at the department of microbiology and cell biology,
centre for infectious disease and research at the Indian
Institute of Science, Bangalore, says, “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.”
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
November in ACS Chemical Biology.
Singh says the new compounds “belong to the ellipticine
plant alkaloid family, which also is active in targeting
cancerous cells”. He adds that the “active compounds
have exerted a very high activity against drug-resistant
M. tuberculosis strains isolated from patients of
Indian origin.” 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.
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TB Statistics
In 2014,
9.6 million people fell ill with TB and 1.5 million died of
it.
More than 95 per cent TB deaths occur in low-
and middle-income countries, and it is among the top five
causes of death for women aged 15 to 44.
In 2014,
an estimated 1 million children were TB infected with and
140,000 children died of it.
TB is a leading
killer of HIV-positive people: in 2014, 1 in 3 HIV deaths
were due to TB.
Globally in 2014, an estimated
480,000 people developed multi-drug resistant TB
(MDR-TB).
Ending the TB epidemic by 2030 is among
the health targets of the newly adopted Sustainable
Development Goals.
*******************
Kate Carroll, chemistry professor at the Scripps Research Institute, Jupiter, Florida, and lead author of the study, stresses 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.”
“These new compounds have shown potent bactericidal activity against active as well as dormant form of drug-susceptible and MDR/XDR strains, as well,” Carroll says. “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.”
Carroll says 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 says.
Singh’s lab has also generated a series of compounds that were found to exert efficient killing of drug-resistant superbugs. He proposes “targeting mechanisms involved in resisting oxidative stress or elevating the levels of oxidative stress inside bacterial cells” as strategies against TB infection. - See more at: http://www.scidev.net/south-asia/tb/news/plant-based-drug-can-fight-resistant-tb.html#sthash.13spDZzf.dpufSome 95 per cent 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, Jupiter, Florida, and lead author of the study, stresses 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.”
“These new compounds have shown potent bactericidal activity against active as well as dormant form of drug-susceptible and MDR/XDR strains, as well,” Carroll says. “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.”
Carroll says 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 says.
Singh’s lab has also generated a series of compounds that were found to exert efficient killing of drug-resistant superbugs. He proposes “targeting mechanisms involved in resisting oxidative stress or elevating the levels of oxidative stress inside bacterial cells” as strategies against TB infection. - See more at: http://www.scidev.net/south-asia/tb/news/plant-based-drug-can-fight-resistant-tb.html#sthash.13spDZzf.dpuf
Some 95 per cent 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, Jupiter,
Florida, and lead author of the study, stresses 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.”
“These new compounds have
shown potent bactericidal activity against active as well as
dormant form of drug-susceptible and MDR/XDR strains, as
well,” Carroll says. “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.”
Carroll says 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 says.
Singh’s lab has also
generated a series of compounds that were found to exert
efficient killing of drug-resistant superbugs. He proposes
“targeting mechanisms involved in resisting oxidative
stress or elevating the levels of oxidative stress inside
bacterial cells” as strategies against TB infection.
Source:
SciDev.Net
