Identification of pyrazinamide-resistant mycobacteria and...

C - Chemistry – Metallurgy – 12 – N

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C12N 15/55 (2006.01) A61K 31/4965 (2006.01) A61K 31/70 (2006.01) A61K 48/00 (2006.01) A61P 31/04 (2006.01) C07H 21/00 (2006.01) C07K 16/40 (2006.01) C12N 9/80 (2006.01) C12Q 1/68 (2006.01) A61K 38/00 (2006.01)

Patent

CA 2254828

Disclosed are methods, probes, primers and kits for identifying pyrazinamide- resistant mycobacteria. These methods can be used to distinguish M. bovis from M. tuberculosis, as well as to identify additional pyrazinamide-resistant mycobacteria. Also disclosed are methods for treating mycobacterial infections by expressing a pncA gene in mycobacteria that infect a mammal, and treating the mammal with pyrazinamide. The invention derives from the discovery of that the molecular basis for pyrazinamide resistance is an alteration in the pncA gene of mycobacteria. The detection of such an alteration is an indicator of PZA-resistant mycobacteria.

La présente invention concerne des procédés, des sondes, des amorces et des nécessaires d'identification des mycobactéries résistantes à la pyrazinamide. De tels procédés permettent de distinguer entre M. bovis et M tuberculosis et d'identifier de nouvelles mycobactéries résistantes à la pyrazinamide. L'invention concerne également des thérapies contre les infections mycobactériennes, lesquelles thérapies consistent à exprimer un gène pncA dans une mycobactérie infectante pour un mammifère, puis à traiter le mammifère avec de la pyrazinamide. L'invention provient de la découverte que la base moléculaire de la résistance à la pyrazinamide est une altération du gène pncA de la mycobactérie. Une telle altération, lorsqu'elle est détectée, est le signe d'une résistance de la mycobactérie à la pyrazinamide.

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