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New Compounds That Kill Dormant TB Bacteria Found

by VR Sreeraman on September 17, 2009 at 12:54 PM
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 New Compounds That Kill Dormant TB Bacteria Found

Scientists have found a pair of compounds that kill dormant tuberculosis bacteria in monkey and lab-grown human cells, according to a study to be published.

The discovery could lead to new drugs that disable the microbe, which lies inactive in approximately two-thirds of the world's poulation.

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Up to now, attempts to eradicate Mycobacterium tuberculosis, the bug that causes TB, have been stymied by a clever mechanism within the bacteria that allows it to withstand attacks by the body's immune system.

Human immune cells produce chemicals which damage or destroy essential proteins within the TB bacteria.

If allowed to accumulate, these crippled proteins would normally kill the bug.
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But a smart molecular machine within the bacteria called the proteasome disposes of the damaged proteins, keeping the TB alive and potentially active.

Researchers led by Carl Nathan of Weill Cornell Medical College in New York set out to find compounds that could disable the proteasome.

But they encountered a problem: human cells also possess the same mechanism, which meant the new drug would have to narrowly target the tuberculosis without harming the host.

The scientists screened 20,000 candidate compounds in search of a proteasome inhibitor and then tested the most promising on kidney cells taken from African green monkeys and on human immune system cells.

Two chemical compounds proved effective, according to the study, published in the British science journal Nature.

"Our studies reveal the detailed mechanism by which these inhibitor molecules work," said Huilin Li, a professor at Stony Brook University in New York and a co-author of the study.

The blocking of the TB proteasome also appeared to be permanent, and was about a thousand times more potent than against human proteasomes, which were largely unaffected, Li said in a statement.

Some 9.27 million people contracted TB in 2007, an increase of about 30,000 over the previous year mainly in line with population growth.

They included some 1.4 million people with HIV/AIDS, compared to an estimated 600,000 in 2006.

More than a quarter of the 1.75 million TB deaths recorded in 2007 are thought to involve a patient with the AIDS virus.

Source: AFP
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