Important note: Information in this article was accurate in 2009. The state of the art may have changed since the publication date.

Reuters NewMedia - September 16, 2009
Julie Steenhuysen

* May offer new approach for antibiotics

CHICAGO, Sept 16 (Reuters) - U.S. researchers have found two compounds that can destroy a defense mechanism in the tuberculosis bacterium that allows it to remain dormant in infected cells, they said on Wednesday.

The compounds, which were among 20,000 studied by the researchers, block the self-defense mechanism but do not harm human cells, raising hope for new and better treatments for TB, they reported in the journal Nature.

Mycobacterium tuberculosis, which causes TB, is the only known bacterium to have a proteasome -- a mechanism that destroys unneeded or damaged proteins.

Most people who are infected remain symptom-free because the bacterium is kept in check within immune system cells.

These cells produce compounds such as nitric oxide, which scientists believe damage or destroy the bacterium's proteins. If allowed to accumulate, the damaged proteins would kill the bacterium -- the proteasome removes them before they fester.

Finding drugs to disable the proteasome and destroy dormant bacteria offers a new way to fight TB, said Carl Nathan of Weill Cornell Medical College in New York, who headed the research team.

"It turns out a lot of them at any moment are hunkered down in the patient," he said.

Nathan's team set out to find compounds that attack Mycobacterium tuberculosis hiding out in cells. To do that, they targeted the proteasome, which basically serves as a garbage disposal, chopping up and discarding damaged proteins.

The trick has been finding highly specific compounds that selectively block only the M. tuberculosis proteasome but do not harm human cells. Nathan's team found two.

Tests in monkey and human cells in the lab showed that the two compounds were not toxic to other cells, or even other bacteria, and the process appeared to be irreversible.

"It's still very basic. These aren't drugs and they have never been tested in an animal or a person," Nathan said.

But he said the study proves it may be possible to make a drug to block this process.

About 1.6 million people die from TB each year, with the disease hitting hardest in African countries that are also struggling to control AIDS. Those infected with HIV are far more likely to contract TB, while the presence of TB makes it more difficult to treat the AIDS virus.

Current drugs for TB are at least four decades old and must be taken over a series of several months.

People often do not take their full regimen of TB drugs, which has in turn spawned drug resistance, making TB more dangerous and more difficult to treat.

(Editing by Maggie Fox and Paul Simao)

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