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PERSISTENT TB


Tuberculosis

Novel Drug Targets Specific to Persistent (Latent) Tuberculosis Infection:  Crystallisation, Structure Determination and Functional Studies
Framework programme:
5
Project number:
QLK2-CT-2002-01682
EC contribution:
€ 800 000
Duration:
36 months
Type:
RS
Starting date:
1 September 2002

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.

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