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NOVSEC-TB


Novel secretion systems of Mycobacterium tuberculosis and their role in host-pathogen interaction.
 
 
Framework programme:
 7
Project number:
201762
EC contribution:
€ 2,800,000
Duration:
42 months
Funding scheme :
Focused Collaborative Research Project : Coordination Action
Starting date:
01/01/2008
Website:
http://www.pasteur.fr/recherche/NOVSEC-TB
 
 

Keywords: Mycobacterium tuberculosis, secretion systems, host-pathogen interaction

Background

Tuberculosis is a major public health threat to the populations of Europe and the world. Mycobacterium tuberculosis, the etiological agent of the disease, can multiply and persist within phagocytic cells and this early event is of primary importance for the outcome of the infection. Secreted, highly immunogenic proteins of M. tuberculosis play a key role in this process.

Aims and expected results

The main objectives of NOVSEC-TB are to use highly innovative approaches in molecular and cell biology, biochemistry, immunology and imagery to elucidate the function and interplay of three families of immunogenic proteins of M. tuberculosis, the ESX, PE and PPE families. It was recently found that the ESX systems constitute novel secretion machineries that export major virulence factors and important diagnostic and protective antigens. While the ESX-1 system is responsible for the secretion of the prototypic ESX proteins, namely the 6 kDa early secreted antigenic target (ESAT-6) and the 10 kDa culture filtrate protein (CFP-10), which are the most important proteins of M. tuberculosis involved in host-pathogen interaction, ESX-5 is implicated in the secretion of PE/PPE proteins. Restriction to pathogenic mycobacteria makes them highly interesting targets for host-pathogen interaction. The ESX-3 system appears to be essential. The proposed approach will generate major insights into the role of these proteins in pathogenicity that are of the utmost importance for the development of new diagnostics, vaccines and therapeutic agents for tuberculosis prevention and control.

NOVSEC will analyse the gene expression networks of these secretion systems, determine the nature and diversity of the effector proteins they secrete, establish their mode of action and sub-cellular localisation, survey potential genetic variation, assess their interaction with the immune system of the host, evaluate the suitability of these systems as drug targets, and screen small molecules for their potential to inhibit ESX-mediated secretion.

The results of NOVSEC are expected to elucidate the important mycobacterial protein secretion systems involved in host-pathogen interaction.

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