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Bacterial Pathway That May Pave Way for TB Treatment Identified

by VR Sreeraman on November 5, 2008 at 12:00 PM
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 Bacterial Pathway That May Pave Way for TB Treatment Identified

In a new study, scientists have uncovered a new pathway in which disease-causing bacteria dodge the host's immune system to survive and grow in the cells that were to destroy them.

Led by Peter Murray, Ph.D., at St. Jude Children's Research Hospital in Memphis, Tenn., and Thomas Wynn, Ph.D., the discovery may pave the way for new treatments and vaccines for tuberculosis (TB) and some other chronic bacterial and parasitic infections.

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Usually, specialized white blood cells called macrophages are the ones to ward off disease-causing bacteria from the body, for which they make compounds like free radical nitric oxide (NO), which can kill pathogens

But, there are still some harmful bacteria, known as intracellular pathogens, which live inside cells and can even survive and replicate within macrophages, by resisting the NO attack.
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Macrophages make a natural NO inhibitor, called arginase, which steals and degrades the material required to make NO, thus limiting how much NO is made.

"The bacteria designed to live inside the cell are highly adapted to their environment. We wanted to determine just how intracellular bacteria were turning on the genes that make arginase, thereby controlling the expression of NO and escaping killing by macrophages," Nature magazine quoted Murray as saying.

It was found that intracellular pathogens increase levels of arginase, which in turn reduces the amount of NO the macrophages produce, enabling intracellular pathogens to survive.

Having persistent intracellular bacteria is quite harmful to people with compromised immune systems, like those with HIV or cancer, who often contract chronic bacterial and parasitic infections.

For checking how arginase production induced by the intracellular bacterium causes TB (Mycobacterium tuberculosis), they generated mice lacking the arginase gene in their macrophages (arginase knockout mice).

When knockout mice were infected with bacteria that are not killed by NO, the scientists found that the lack of arginase did not affect the macrophages' ability to clear the infection.

"This work suggests that targeting arginase may be helpful in treating chronic, intracellular bacterial and parasitic infections," said Wynn.

The researchers are working towards determining what other parts of the immune system are affected when arginase is blocked.

The findings of the study appear in the journal Nature Immunology.

Source: ANI
SRM/SK
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