A Novel Method of Interfering with Iron Uptake by Mycobacterium Tuberculosis and Related Organisms

Web Published:
12/1/2011
Description:

Princeton Invention # 04-2103

           

Researchers in the Chemistry Department at Princeton University have discovered a novel pathway which may allow for a new pharmacological approach to the control of tuberculosis.

 

The rational discovery of drugs requires prior knowledge of metabolic pathways. Usually this involves identifying the function of certain enzymes in a metabolic pathway of interest and then finding inhibitors of those enzymes. In contrast, Princeton researchers have discovered a new mechanism by which mycobacteria exploit membrane trafficking pathways of the host macrophage to acquire the iron that is known to be necessary for survival and proliferation within the host. Since iron deprivation is known to be a natural bacteriostatic strategy, knowledge of this pathway and the development of techniques for elucidating this and related pathways will allow for the identification of agents that either interfere with iron acquisition or use this pathway to actively deliver antibacterial drugs to mycobacterium while it is inside the macrophage.

 

The technology covers two important discoveries regarding the mechanisms of iron acquisition by M. tuberculosis and other pathogens that use amphiphilic or lipophilic siderophores. Together these discoveries could provide new avenues of therapeutic intervention with these pathways.

 

Tuberculosis is the number one cause of death from an infectious disease in the World. In addition to the 8 million cases of active disease every year, over a billion people are latently infected with M. tuberculosis, running a 10% lifetime risk of developing active disease (World Health Organization tuberculosis fact sheet; http://www.who.int). The ability of this organism to infect an extraordinary number of people, combined with the widespread emergence of multi-drug resistant strains, has lead to the placement of M. tuberculosis on the National Institute of Allergy and  Infectious Diseases (NIAID) list of Biodefense and Emerging Infectious Disease Threat Agents.

 

Selected References:

 

Mycobactin-mediated iron acquisition within macrophages, Nature Chemical Biology, Luo, M., Fadeev, E.A. & Groves, J.T. Nature Chemical Biology 1, 149-153 (2005)

 

Getting the Iron Out, Nature Chemical Biology, Barry, C.E., Boshoff, H., Volume 1 Number 3, 127-128 August 2005

 

 

Princeton University is currently seeking industrial collaborators to further develop and commercialize this technology.  Patent protection is pending.

 

For more information on Princeton University Invention # 04-2103, please contact:

               

 

                                Laurie Tzodikov

                                Office of Technology Licensing and Intellectual Property

                                Princeton University

                                4 New South Building

                                Princeton, NJ 08544-0036

                                (609) 258-7256

                                (609) 258-1159 fax

                                tzodikov@princeton.edu

Patent Information:
For Information, Contact:
Laurie Tzodikov
Licensing Associates
Princeton University
tzodikov@Princeton.EDU
Inventors:
John Groves
Keywords:
Chemistry