Potential Therapeutic Target for Tuberculosis Identified

by VR Sreeraman on Aug 3 2008 9:01 AM

Researchers from Weill Cornell Medical College claim to have identified a potential therapeutic target for tuberculosis.

The study led by Omar H. Vandal, a postdoctoral fellow in the lab of study co-senior author Dr. Sabine Ehrt, associate professor of microbiology and immunology at Weill Cornell Medical College, has found a membrane protein called Rv3671c, which is critical to bacteria's defence against immune cell acidification during Mycobacterium tuberculosis infection.

"Using novel techniques, we have identified a key membrane protein that's essential to the defense that M. tuberculosis mounts against the acidic environment of immune cells called macrophages," Nature quoted the researchers as saying.

"Without this protein, called Rv3671c, the bacterium becomes vulnerable to acidification and is killed," they added.

Dr. Carl F. Nathan, also a senior author of the study, R.A. Pritchett Professor of Microbiology and chairman of the Department of Microbiology and Immunology at Weill Cornell said, " M. tuberculosis does not depend on Rv3671c under standard growth conditions in the test tube, so it has been overlooked as a candidate drug target.

"However, when M. tuberculosis infects the host, then the Rv3671c protein becomes essential," added Dr. Ehrt.

"This is an example of a new class of potential targets for anti-infective agents," said Dr. Nathan, "those that the pathogen only needs in order to survive in the host environment."

The researchers focussed their study over changes in the pH (acidity) of the phagosome, a structure that macrophages use to consume and destroy pathogens, including bacteria.

"As part of this process, the phagosome becomes acidic, which is thought to contribute to its ability to break down and destroy the pathogen," said Dr. Ehrt.

"However, M. tuberculosis appears to survive the acidification process, keeping its own internal pH stable," she added.

"What we observed was pretty amazing - without functioning Rv3671c, the mutant bacterium was easily destroyed in a low-pH environment, both in culture and inside the more acidic environment of the macrophage. This revealed a new point of vulnerability for the bacterium," said Dr. Vandal.

Researchers hope that targeting an element involved directly in the infective process would help in developing new drugs for treating the global health threat.

The study is published in Nature Medicine.