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TB prevention cluster


Tuberculosis

New Strategies for Treatment and Prevention of Mycobacterial Diseases
Framework programme:
5
Project number:
QLK2-CT-2000-01761
EC contribution:
€ 2 000 000
Duration:
48 months
Type:
RS
Starting date:
1 December 2000

Keywords: Tuberculosis; drug development; treatment; prevention; drug resistance; molecular genetics; crystallography; biochemistry

Summary:

The overall objective of the cluster project is to establish a European framework to develop new strategies for the treatment of mycobacterial diseases. The project will study the mycobacterial cell wall structure to overcome the permeability barrier mediating innate drug resistance and characterise mycobacterial targets for future drug design. Integration of these activities, with the participation of leading research groups in Europe, is essential for completing the goal of developing novel approaches for control of infections with Mycobacterium tuberculosis.

Problem:

Tuberculosis, the white plague of former times, represents a major health problem worldwide. It is still the single largest cause of death amongst all bacterial infections: 3 million people die each year of tuberculosis, and one third of the world’s population is being infected with Mycobacterium tuberculosis, the causative bacterial agent. A particularly threatening development has been the emergence of strains of M. tuberculosi,s which are resistant to all of the front-line antituberculous drugs. There is, therefore, an urgent need to tackle the problem of treatment with infections with M. tuberculosis, both with an understanding of drug resistant mechanisms and working towards a development of new drugs with antimycobacterial activity.

One of the major problems in developing antibiotics with antimycobacterial activity is the unusual mycobacterial cell wall with an intrinsically low permeability, making these microorganisms resistant to most commonly used antibacterial agents. This permeability barrier serves as a rate-limiting step in drug uptake and is controlled by properties of the cell envelope.

Many of the existing antituberculous drugs target the synthesis of the mycobacterial cell wall, and the unusual structure of the cell wall makes this a particularly fertile area for developing new antituberculosis agents. More recently, the availability of the M. tuberculosis genome sequence has provided unprecedented insights into physiological processes, which may point toward completely novel drug targets.

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