Keywords: Latent tuberculosis; drug targets; 3Dstructure; inhibitors; drug design
The aim of this project is to solve the 3D structure of several sterilising drug targets, some of which have been identified by this consortium recently. These specific drug targets are associated with persistence of Mycobacterium tuberculosis. The project’s approach would be to target proteins that are active in dormant cells. The structural elucidation of such drug targets would lead to the development of totally novel antibiotics, with completely new modes of action, which are active against stationary phase persistent Mycobacterium tuberculosis. These antibiotics will shorten the duration of chemotherapy and/or synergise with existing antibiotics in humans by reducing bacterial sub-populations, which are tolerant to conventional antimicrobials and thus control the reactivation of TB.
M. tuberculosis remains the leading cause of death worldwide from an infectious agent and is responsible for nearly 3 million deaths every year. About one-third of the world population is infected with M. tuberculosis, 10% of whom will develop the disease at some point in their lives. Currently available antibiotics are completely ineffective against persistent bacteria.
The approach is to focus on persistence-associated proteins and determine the structure of these proteins. The main thrust of this project is in drug design, based on the molecular 3-dimensional structure of drug targets for latent TB.
The knowledge on drug targets for latent tuberculosis that is generated in this project is expected to result in the development of specific inhibitors/antibiotics for tuberculosis. These antibiotics will shorten the duration of chemotherapy and/or synergise with existing antibiotics in humans by reducing bacterial sub-populations, which are tolerant to conventional antimicrobials.
It is anticipated that the information generated will be used for drug design and development in collaboration with the pharmaceutical industry.
|Official Address||Other Information|
|2||Anthony Coates||Medical Microbiology |
St George’s Hospital Medical School
UK-SW17 0RE London
|Tel: +44 208 725 5725 |
Fax: +44 208 672 0234
|3||Gunter Schneider||Department of Medical Biochemistry and Biophysics (MBB) |
Scheeles väg 2
SE-171 77 Stockholm
|Tel: +46 8 08 728 7675 |
Fax: +46 8 08 32 7626
|4||Paul C. Driscoll||Department of Biochemistry and Molecular Biology |
University College London
UK-WC1E 6BT London
|Tel: +44 207 679 7035 |
Fax : +44 207 679 7193
|5||Han-Jürgen Hecht||Struckturforschung |
GBF-German Research Centre for Biotechnology
Mascheroder Weg 1
|Tel: +49 531 618 1369 |
Fax: +49 531 618 1355