Navigation Links
Researchers discover metabolic vulnerability in TB and potential drug target

NEW YORK (May 10, 2010) -- Tuberculosis (TB) has been present in humans since ancient times. The origins of the disease date back to the first domestication of cattle, and skeletal remains show prehistoric humans (4,000 B.C.) had TB. Although relatively rare in the United States, it is the single leading bacterial cause of death worldwide. Approximately 8 million people are infected each year and 2 million people die from TB.

The cause of tuberculosis is Mycobacterium tuberculosis (Mtb), a slow-growing aerobic bacterium that divides every 16 to 20 hours. Scientists know that carbon metabolism plays a significant role in the ability of Mtb to replicate and persist in the body and that fatty acids are the major source of carbon and energy during infection. However, the specific enzymes required for the metabolism of fatty acids have not been completely defined.

New research conducted at Weill Cornell Medical College and published online in the Proceedings of the National Academy of Sciences (PNAS) sheds light on a previously unrecognized aspect of fatty acid metabolism that could potentially lead to new targets for drug therapy. A team led by Dr. Sabine Ehrt, professor of microbiology and immunology at Weill Cornell Medical College, reported that Mtb relies primarily on gluconeogenic substrates for in vivo growth and persistence, and that phosphoenolpyruvate carboxykinase (PEPCK) plays a pivotal role in the growth and survival of Mtb during infections in mice, making PEPCK a potential target for drugs that fight tuberculosis.

Dr. Ehrt and her colleagues found a way to silence the gene encoding PEPCK in Mtb during mouse infections to assess the importance of gluconeogenesis for Mtb's ability to maintain a chronic infection. According to Dr. Ehrt, "Silencing a gene when the pathogen is not or only slowly replicating, after an infection has established, is an important tool for studying diseases such as TB, which can be dormant for years only to become active again years later."

Dr. Ehrt, the lead author on the paper, conducts basic research on the pathogenesis of tuberculosis. She and her team investigate the role of the macrophage in the immune response to Mtb and the molecular mechanisms used by the pathogen to establish and maintain persistent infections. A goal of Dr. Ehrt's research is to validate novel drug targets that may facilitate the development of new therapies against active and chronic TB.

"Tuberculosis is very difficult to treat," says Dr. Erht. "It is especially challenging as the infection can lay dormant in the body even though there are no symptoms. We investigated the metabolic requirements of Mtb during acute and chronic infections and found that the gluconeogenic enzyme PEPCK is critical for both."

The study used a novel mass spectrometry-based metabolic profiling tool, developed at Weill Cornell (in collaboration with Agilent Technologies) by Dr. Kyu Rhee to biochemically examine Mtb carbon metabolism. The tool has provided the first direct insights into the metabolic architecture of Mtb. Dr. Rhee is a co-author and assistant professor of medicine, microbiology & immunology, and the Hearst Clinical Scholar in Microbiology & Infectious Diseases at Weill Cornell Medical College.

Dr. Ehrt hopes that her work will eventually lead to new drug therapies to treat tuberculosis. "Although the current treatments we have to treat Mtb are effective, the treatment times are too long and the regimens too complex. This leads to treatment failures, due to poor adherence and multidrug resistance. We need new, safer drugs that work faster to eliminate tuberculosis."


Contact: Andrew Klein
New York- Presbyterian Hospital/Weill Cornell Medical Center/Weill Cornell Medical College

Related biology news :

1. Researchers use entire islands in the Bahamas to test survival of the fittest
2. Researchers discover genetic link between both types of ALS
3. UBC researchers design new biomaterial that mimics muscle elasticity
4. UCLA researchers show how worlds smallest coffee ring may help biosensors detect disease
5. Researchers find melanoma not caused by early UVA light exposure
6. Bugging out: NC State researchers help track wayward pests through mapping
7. Aboriginal hunting and burning increase Australias desert biodiversity, Stanford researchers find
8. Ben-Gurion U researchers isolate microalgal strain that could reduce cholesterol
9. JGH researchers help pinpoint osteoporosis genes
10. Researchers recommend pregnant women take 4,000 IU vitamin D a day
11. Gene therapy sets stage for new treatments for inherited blindness, Penn veterinary researchers say
Post Your Comments:
(Date:4/28/2016)... and BANGALORE, India , April 28, 2016 ... a product subsidiary of Infosys (NYSE: INFY ), ... a global partnership that will provide end customers ... mobile banking and payment services.      (Logo: ... innovation area for financial services, but it also plays a ...
(Date:4/26/2016)... LONDON , April 26, 2016 /PRNewswire/ ... Systems, a product subsidiary of Infosys (NYSE: ... partnership to integrate the Onegini mobile security platform ... ) The integration ... security to access and transact across channels. Using ...
(Date:4/19/2016)... The new GEZE SecuLogic access ... "all-in-one" system solution for all door components. It can ... door interface with integration authorization management system, and thus ... minimal dimensions of the access control and the optimum ... offer considerable freedom of design with regard to the ...
Breaking Biology News(10 mins):
(Date:6/27/2016)... ... June 27, 2016 , ... Parallel 6 , the leading software ... Clinical Reach Virtual Patient Encounter CONSULT module which enables both audio and ... clinical trial team. , Using the CONSULT module, patients and physicians can schedule a ...
(Date:6/24/2016)... 2016  Regular discussions on a range of subjects including ... two entities said Poloz. Speaking at a lecture ... , he pointed to the country,s inflation target, which is ... "In certain areas there ... common economic goals, why not sit down and address strategy ...
(Date:6/23/2016)... ... 2016 , ... UAS LifeSciences, one of the leading manufacturers ... Probiotics, into Target stores nationwide. The company, which has been manufacturing high quality ... list of well-respected retailers. This list includes such fine stores as Whole Foods, ...
(Date:6/23/2016)... MA (PRWEB) , ... June 23, 2016 , ... ... Peel Plate® YM (Yeast and Mold) microbial test has received AOAC Research Institute ... platform of microbial tests introduced last year,” stated Bob Salter, Vice President of ...
Breaking Biology Technology: