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PERSISTENT TB
TUBERCULOSIS
Framework programme: 5
Project number:
QLK2-CT-2002-01682
EC contribution: € 800 000
Duration: 36 months
Type: RS
Starting date: 1 September 2002
Graphic element Novel Drug Targets Specific to Persistent (Latent) Tuberculosis Infection:  Crystallisation, Structure Determination and Functional Studies
Keywords: Latent tuberculosis; drug targets; 3Dstructure; inhibitors; drug design

Summary:

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.

Problem:

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.

Aim:

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.

Expected results:

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.

Potential applications:

It is anticipated that the information generated will be used for drug design and development in collaboration with the pharmaceutical industry.

Coordinator:

Mahavir Singh
Lionex GmbH
Mascheroder Weg 1b
38124 Braunschweig
Germany
Tel: +49 531 260 1266
Fax: +49 531 260 1159
E-mail: info@lionex.de
Website: http://www.lionex.de

Partners:

Principal
Scientific
Participants
Official Address Other Information
2Anthony CoatesMedical Microbiology
St George’s Hospital Medical School
Cranmer Terrace
UK-SW17 0RE London
United Kingdom
Tel: +44 208 725 5725
Fax: +44 208 672 0234
E-mail: acoates@sghms.ac.uk
3Gunter SchneiderDepartment of Medical Biochemistry and Biophysics (MBB)
Karolinska Institutet
Scheeles väg 2
SE-171 77 Stockholm
Sweden
Tel: +46 8 08 728 7675
Fax: +46 8 08 32 7626
E-mail: gunter@alfa.mbb.ki.se
4Paul C. DriscollDepartment of Biochemistry and Molecular Biology
University College London
Gower Street
UK-WC1E 6BT London
United Kingdom
Tel: +44 207 679 7035
Fax : +44 207 679 7193
E-mail: driscoll@biochemistry.ucl.ac.uk
5Han-Jürgen HechtStruckturforschung
GBF-German Research Centre for Biotechnology
Mascheroder Weg 1
DE-38124 Braunschweig
Germany
Tel: +49 531 618 1369
Fax: +49 531 618 1355
E-mail: hjh@gbf.de

 
 
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