Suicide and poison may save millions

(World Health Organization 2010)

March 24 is World Tuberculosis (TB) Day, and this year's focus is on innovation with the looming deadline to stop TB by 2010. Groundbreaking research from Einstein University has found two novel approaches to destroy the bacteria that causes TB ( Mycobacterium tuberculosis) and claims over two million lives annually.

"This approach is totally different from the way any other anti-TB drug works," said William R. Jacobs, Jr., Ph.D., the study's senior author and professor of microbiology & immunology and of genetics at Einstein. "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."

Jacobs and a team of researchers published their findings on March 21 in Nature Chemical Biology, a respected international biology and chemistry journal, elucidating how restraining GlgE, a unique enzyme that does not exist in humans, the bacteria became "suicidal self-poisoning" damaging the bacterial DNA and killing TB bacteria in both in vitro and animal studies.

Jacobs explained, "We were amazed when we knocked out GlgE that we saw this DNA damage response. That's usually a very effective way to kill bacteria, when you start damaging the DNA."

GlgE is safe to inactivate with a drug and, with the help of trehalose, a dietary sugar, could be used to make an anti-GlgE drug more potent. "This pathway has never previously been targeted by antimicrobials and offers a treatment option very different from antibiotics in use," concluded Jacobs.

Full study, "Self-Poisoning of Mycobacterium tuberculosis by targeting GlgE in an a-glucan pathway": http://www.nature.com/nchembio/journal/vaop/ncurrent/full/nchembio.340.html More information on TB innovation and World TB Day: http://www.stoptb.org/events/world_tb_day/2010/Video with researcher: http://www.youtube.com/EinsteinCollegeofMed#p/a/u/0/U6-ba-ijTpQ