Navigation Links
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 of TB bacteria grown in Petri dishes as well as in infected mice.

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

The researchers discovered a second way of killing TB after observing a crucial connection between their novel alpha glucan pathway and a second pathway that also synthesizes alpha glucans.

When the researchers knocked out one of the other enzymes in their novel pathway, the pathway's shutdown didn't kill the bacteria; similarly, inactivating an enzyme called Rv3032 in the second alpha glucan pathway failed to kill the microbes. But inactivating both of those enzymes caused what the researchers term synthetic lethality: two inactivations that separately were nonlethal but together cause bacterial death.

"The bacteria that cause TB need to synthesize alpha glucans," notes Dr. Jacobs. "And from the bacterial point of view, you can't knock out both of these alpha glucan pathways simultaneously or you're dead. So if we were to make drugs against GlgE and Rv3032, the combination would be extremely potent. And since TB bacteria need both of those alpha glucan pathways to live, it's very unlikely that this combination therapy would leave behind surviving bacteria that could develop into resistant strains."

Dr. Jacobs adds that findings from this study could also enhance treatment of diseases caused by other species of mycobacteria. Leprosy, for example, which still occurs in the U.S. and other countries, is caused by a mycobacterium related to TB. Treating leprosy now involves using several different drugs, some of which are also used to treat tuberculosis.


'/>"/>

Contact: Deirdre Branley
sciencenews@einstein.yu.edu
718-430-3101
Albert Einstein College of Medicine
Source:Eurekalert

Related biology news :

1. Einstein researcher receives NIH grant to explore epigenetic regulation of the human genome
2. Einstein researchers receive grants totaling $700,000 for innovative breast cancer research
3. Feinstein researchers develop new genetic method and identify novel genes for schizophrenia
4. In scientific first, Einstein researchers correct decline in organ function associated with old age
5. Einstein researchers develop a new way to study how breast cancer spreads
6. Einstein researchers develop technique to count messages made by single genes
7. Einstein scientists receive $10 million NIH grant
8. Empire State Stem Cell Board awards $12.7 million to Albert Einstein College of Medicine
9. Einstein and Pitt researchers develop new TB test that will dramatically cut diagnosis time
10. NIH funds research center for womens reproductive health at Einstein
11. Einstein researchers devise a fast and sensitive way to detect ricin
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:2/1/2016)... 1, 2016  Today, the first day of American ... to develop a first of its kind workplace health ... Watson. In the first application of Watson ... IBM ), and Welltok will create a new offering ... cognitive analytics, delivered on Welltok,s health optimization platform. The ...
(Date:1/25/2016)... BELL, Pa. , Jan. 25, 2016   Unisys Corporation ... recognition system at John F. Kennedy (JFK) International Airport, ... Border Protection (CBP) identify imposters attempting to enter ... do not belong to them. pilot testing of ... out initially at three terminals at JFK during January 2016. ...
(Date:1/21/2016)... January 21, 2016 ... new market research report "Emotion Detection and Recognition Market by ... Tools (Facial Expression, Voice Recognition and Others), Services, ... forecast to 2020", published by MarketsandMarkets, the global ... reach USD 22.65 Billion by 2020, at a ...
Breaking Biology News(10 mins):
(Date:2/5/2016)... MANASSAS, Va. , Feb. 5, 2016 ... organization, is poised to assist the medical and life ... concerns around Zika Virus infection.   CDC ... --> Zika virus is a single-stranded ... also includes the West Nile, Dengue and Chikungunya Viruses. ...
(Date:2/4/2016)... San Francisco, CA (PRWEB) , ... February 04, ... ... future of enterprise talent development and compliance training, today announced an interactive ... on Morf Playbook™. The RAPS (Regulatory Affairs Professional Society) accredited interactive course ...
(Date:2/4/2016)... , Feb. 4, 2016 Beike Biotechnology, ... various medical institutions attended a ceremony in late 2015 ... personalized cell therapy in 2016. --> ... Clinical Translation Platform for Personalized Cell Therapy" was hosted ... Cell Production Center, both subsidiaries of Beike Biotechnology Co., ...
(Date:2/4/2016)... 2016  Spherix Incorporated (Nasdaq: SPEX ) -- an intellectual ... of intellectual property, today provided an update on the ... District of Texas and announcing ... Inter Partes Re-examination ("IPR") proceedings that VTech and ... was initiated on only certain claims of two of ...
Breaking Biology Technology: