Reduction in the virulence of mycobacterium tuberculosis and...

C - Chemistry – Metallurgy – 12 – N

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C12N 1/20 (2006.01) C07K 14/35 (2006.01) C12N 1/36 (2006.01)

Patent

CA 2456007

The construction of a mutant in the phoP gene by means of homologous recombination from a clinically isolated Mycobacterium tuberculosis reduces the virulence thereof in mouse bone marrow macrophage. Moreover, the phoP mutant reduces the virulence thereof in the experimental mouse model. Said phoP mutant can persist without being eliminated both in the macrophage and in the mouse. Mice inoculated with the phoP mutant are protected against M. tuberculosis infection. The use of mutants of mycobacteria in which the phoP gene or the genes regulated by phoP have been inactivated are candidates for vaccines against human and animal tuberculosis as well as possible recombinant vaccines against other pathogens.

La construction d'un mutant dans le gène <i>phoP</i> par recombinaison homologue à partir de <i>Mycobacterium tuberculosis</i> isolé cliniquement, diminue sa virulence dans le macrophage de la moelle osseuse du rat. De plus, le mutant <i>phoP</i> diminue sa virulence dans le modèle expérimental du rat. Ce mutant <i>phoP</i> peut persister sans être éliminé aussi bien dans le macrophage que dans le rat. Des rats auxquels le mutant <i>phoP</i> a été inoculé sont protégés contre l'infection par<i>M. tuberculosis</i>. Les mutants de mycobactéries dans lesquels on a inactivé le gène <i>phoP</i> ou les gènes régulés par <i>phoP</i>, sont candidats à des vaccins contre la tuberculose humaine et animale, et éventuellement, des vaccins recombinants contre d'autres agents pathogènes.

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