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Effect of genetic variation in Mycobacterium tuberculosis on vaccine escape and the acquisition of drug resistance

Obiettivo

Tuberculosis (TB) remains a major public health threat, still emerging in some areas of the world. The major tools to control the TB epidemic are worldwide implementation of the directly observed therapy short course (DOTS) programme and BCG vaccination. However, these methods to control TB are not ideal. The efficacy of BCG vaccination is doubtful and significant problems with resistance against anti-TB drugs have emerged. These problems could be fuelled by the selection of more adapted variants of Mycobacterium tuberculosis.

The proposed project aims to further investigate the hypothesis on the selection of M. tuberculosis genotypes by the measures used to control the epidemic; anti-TB treatment and BCG vaccination. These selection mechanisms will be investigated by studying the population structure of M. tuberculosis in various regions by using DNA fingerprint tools. Trends in the dynamics of the population structure (emerging genotypes) will be identified. The association of the various genotypes with drug resistance or possible vaccine escape will be studied. Furthermore, the influence of genetic variability among M. tuberculosis strains on the virulence and immune response induced by these strains and the protection of various vaccines against these strains will be studied in vivo.

In addition, the effect of genetic variation in the M. tuberculosis genome on bacterial adaptability and response to stress will be studied. This will involve in vitro studies of the phenotypic effect of specific drug resistance and other mutations, with an emphasis on mutations in (putative) DNA repair genes. Insights into the adaptation of M. tuberculosis in response to control efforts should allow improved strategies for treatment and control and possibly reveal new targets for intervention.

Campo scientifico (EuroSciVoc)

Programma(i)

Argomento(i)

Invito a presentare proposte

FP6-2005-LIFESCIHEALTH-6
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Meccanismo di finanziamento

STREP - Specific Targeted Research Project

Coordinatore

NATIONAL INSTITUTE OF PUBLIC HEALTH AND THE ENVIRONMENT
Contributo UE
Nessun dato
Costo totale
Nessun dato

Partecipanti (10)