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New dual recognition mechanism discovered in tuberculosis
Date:9/9/2010

advantage. The paradox here is that the MTB molecule, LprG, stimulates TLR2, one of the major receptors we have to identify disease-causing microorganisms. In this case, too much stimulation through TLR2 actually favors MTB by causing parts of the immune response to shut down," explains W. Henry Boom, MD, professor of medicine and director of the Tuberculosis Research Unit at Case Western Reserve School of Medicine.

The new studies show that the potency of LprG to induce these responses is explained by its combination of two mechanisms to activate TLR2: first, by directly stimulating TLR2 and, second, by serving as a carrier to deliver other molecules that stimulate TLR2. This dual mechanism may drive stronger regulation of immune responses by MTB, and future vaccine development may be enhanced by designing approaches to use such mechanisms. Furthermore, the work indicates that LprG contributes to the assembly of the bacterial cell wall, suggesting that it may be possible to develop molecules to interfere with LprG function and potentially serve as new antibiotics to fight TB. The development of new antibiotics is an increasingly important goal, since resistance to existing antibiotics is becoming widespread.

A multi-institutional partnership contributed to the overall success of this research initiative. Two important collaborative groups were led by James C. Sacchettini, PhD, Texas A&M University and D. Branch Moody, MD, Harvard Medical School. In addition, the project was spearheaded by Michael G. Drage and Nicole D. Pecora, two Case Western Reserve students in the MSTP Program, granting dual MD and PhD degrees, in collaboration with Jennifer Tsai, a graduate student in Dr. Sacchettini's group.

"Our research team is composed of several collaborative groups that each contributed key components to this project. The synergistic way in which the team interacted was a perfect example of scientists working together to advance the study of
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Contact: Jessica Studeny
jessica.studeny@case.edu
216-368-4692
Case Western Reserve University
Source:Eurekalert

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