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