PEPCK (phosphoenolpyruvate carboxykinase) a potential target for drugs that fight tuberculosis.

 In continuation of my update on tuberculosis and drug discovery ..... A new  research conducted at Weill Cornell Medical College 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 see picture) 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.

 "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." says Dr.Ehrt...

 It is especially challenging as the infection can lay dormant in the body even though there are no symptoms. Researchers investigated the metabolic requirements of Mtb during acute and chronic infections and found that the gluconeogenic enzyme PEPCK is critical for both.

Interestingly, 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. As per the claim by the researchers,  the tool has provided the first direct insights into the metabolic architecture of Mtb.

 Though the current treatments used  to treat Mtb are effective, the treatment times are too long and the regimens too complex, which  leads to treatment failures (due to poor adherence and multi drug resistance).   We need new, safer drugs that work faster to eliminate tuberculosis.  Dr. Ehrt hopes that her work will eventually lead to new drug therapies to treat tuberculosis.....

Ref : http://www.pnas.org/content/early/2010/04/26/1000715107