Identification of pyrazinamide-resistant mycobacteria and methods for treating mycobacterial infections
AssigneeThe Johns Hopkins University
InventorsYing Zhang, Angelo Scorpio
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Abstract
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.
Claims13
An isolated nucleic acid encoding an M. tuberculosis pyrazinamidase (PZase) polypeptide having the amino acid sequence of SEQ. ID NO:
- 2 or a fragment thereof having biological activity of SEQ. ID No. 2.
An isolated nucleic acid encoding a conservative variation of SEQ. ID NO:
- 2 and having a biological activity of SEQ. ID NO:
- 2.
An isolated nucleic acid encoding an altered M. tuberculosis PZase polypeptide having the sequence of SEQ. ID NO:
- 2, except for a -1 frameshift at amino acid position 96.
An isolated nucleic acid encoding an altered M. tuberculosis PZase polypeptide having the amino acid sequence of SEQ ID NO:
- 2 except for a -1 frameshift at amino acid position.
An isolated nucleic acid encoding an altered M. tuberculosis PZase polypeptide having the amino acid sequence of SEQ.
- ID NO:
- 2, except for a histidine residue at amino acid position.
An isolated nucleic acid encoding an altered M. tuberculosis PZase polypeptide, wherein the nucleic acid encodes a serine residue at amino acid position 138 of SEQ. ID NO:
- 2.
An isolated nucleic acid encoding an altered M. tuberculosis PZase polypeptide, wherein the nucleic acid encodes a polypeptide having the sequence of SEQ. ID. NO:
- 2, except for a proline residue at amino acid position 141.
Dependencies are inferred from the claim text.