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Einstein researchers discover 2 new ways to kill TB
Date:3/21/2010

March 21, 2010 ─ (BRONX, NY) ─ Researchers at Albert Einstein College of Medicine of Yeshiva University have found two novel ways of killing the bacteria that cause tuberculosis (TB), a disease responsible for an estimated two million deaths each year. The findings, published in the March 21 online issue of Nature Chemical Biology, could lead to a potent TB therapy that would also prevent resistant TB strains from developing.

"This approach is totally different from the way any other anti-TB drug works," says William R. Jacobs, Jr., Ph.D., the study's senior author and professor of microbiology & immunology and of genetics at Einstein, as well as a Howard Hughes Medical Institute investigator. "In the past few years, extremely drug resistant strains of TB have arisen that can't be eliminated by any drugs, so new strategies for attacking TB are urgently needed."

Tuberculosis is caused by the bacterial species Mycobacterium tuberculosis. In searching for a new Achilles' heel for M. tuberculosis, Dr. Jacobs and colleagues focused on an enzyme called GlgE. Previous research had suggested that GlgE might be essential for the growth of TB bacteria. GlgE would also be an excellent drug target because there are no enzymes similar to it in humans or in the bacteria of the human gut.

The GlgE research revealed a previously unknown enzymatic pathway by which TB bacteria convert the sugar trehalose (consisting of two glucose molecules) into longer sugar molecules known as alpha glucans building blocks that are essential for maintaining bacterial structure and for making new microbes through cell division. GlgE was the third of four enzymes involved in this pathway leading to alpha glucans molecules.

Sure enough, when the researchers inhibited GlgE, the bacteria underwent "suicidal self-poisoning": a sugar called maltose 1-phosphate accumulated to toxic levels that damaged bacterial DNA, causing the death
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Contact: Deirdre Branley
sciencenews@einstein.yu.edu
718-430-3101
Albert Einstein College of Medicine
Source:Eurekalert

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