Targeting of Triacylglycerol Synthesis or Metabolism for Tuberculosis Treatment

Targeting of Triacylglycerol Synthesis or Metabolism for Tuberculosis Treatment
PDF Version
Background Tuberculosis (TB), one of the biggest killers among the infectious diseases, poses a major public health problem mostly in the developing world with 8 million new cases and 2 million deaths a year (World Health Organization; 2005). Mycobacterium tuberculosis, the causative agent of TB, is inhaled by people as an aerosol emanating from active TB patients. Usually, only a small fraction of the people (~5 %) thus infected develop active TB, while the rest carry a latent infection for the rest of their lives until reactivation of the pathogen occurs upon weakening of the immune system. The ability of the pathogen to go into a latent/dormant non-replicating state, with very low metabolic activity and phenotypic resistance to all of the currently available anti-tuberculosis drugs makes TB eradication an extremely difficult challenge. The inventors have discovered that triacylglycerol can be used as an energy source by M. tuberculosis in dormancy, thus its synthesis or metabolism could be an ideal drug target against latent TB. The current invention describes the use of M. tuberculosis triacylglycerol synthase or triacylglycerol hydrolase to screen for therapeutic agents useful in the treatment of M. tuberculosis infections. Application The current invention presents a screening method for identifying novel anti-TB agents useful in treating TB infections. The screening method could identify novel therapeutic agents that will effectively address the problem of multidrug resistant (MDR) strains of bacteria. Invention The current invention allows for the screening of various anti-TB therapeutic agents based on their ability to bind M. tuberculosis triacylglycerol synthase or triacylglycerol hydrolase polypeptides. Advantages • Novel and low cost method to screen possible agents effective against latent/dormant TB Lead Inventor Pappachan E. Kolattukudy, Ph.D. Selected References Sirakova TD, Dubey VS, Deb C, Daniel J, Korotkova TA, Abomoelak B, Kolattukudy PE. Identification of a diacylglycerol acyltransferase gene involved in accumulation of triacylglycerol in Mycobacterium tuberculosis under stress. 2006; Microbiology. 152(Pt 9): 2717-2725. Deb C, Daniel J, Sirakova TD, Abomoelak B, Dubey VS, Kolattukudy PE. A novel lipase belonging to the hormone-sensitive lipase family induced under starvation to utilize stored triacylglycerol in Mycobacterium tuberculosis. 2006; J Biol Chem. 281(7): 3866-3875. Contact Attn: Svetlana Shtrom, Ph.D., MBA University of Central Florida Office of Research and Commercialization 12201 Research Parkway, Suite 501 Orlando, Fl 32826-3246 Phone: 407.823.5150 Fax: 407.823.3299 sshtrom@mail.ucf.edu UCF ID# 6985, 6989