Scientists Uncover New Anti-TB Compounds

ITHICA – Scientists from Weill Cornell Medical College have identified certain compounds that would inhibit the sophisticated mechanism used by tuberculosis bacteria for surviving dormant in infected cells.

The researchers said most of the people infected with TB remain symptom-free because the Mycobacterium tuberculosis, the disease-causing bacteria, is kept in check within immune system cells.

These cells produce compounds such as nitric oxide, which scientists believe damage or destroy the bacteria’s proteins. If these compounds are allowed to accumulate, the damaged proteins would kill the bacteria.

However, a protein-cleaving complex known as a proteasome breaks down that damaged proteins and allows the bacteria to remain dormant.

The researchers suggest that finding drugs to disable the proteasome would be a new way to fight TB.

During the study, the researchers examined 20,000 compounds for TB proteasome inhibition activity, and identified and synthesized a group of inhibitors, which they then tested for their ability to inhibit the proteasome inside the mycobacteria.

“We believe these findings represent a new approach for developing antibiotics in the fight against TB,” Nature magazine quoted Dr. Carl Nathan, senior author and chairman of the Department of Microbiology and Immunology, R.A. Rees Pritchett Professor of Microbiology and director of the Abby and Howard P.

Milstein Program in Chemical Biology of Infectious Disease at Weill Cornell Medical College, as saying

“This is important because we are running out of effective antibiotics that are currently available. There are few drugs that successfully combat TB in its dormant stage, which makes the bacterium so resilient in the body.

“More important, there are many antibiotics that kill bacteria by blocking the synthesis of proteins, but there are none that kill bacteria by interfering with protein breakdown, as we have found here,” Nathan added.

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