ALTERATIONS IN THE GENES pncA and rpsA AND PYRAZINAMIDASE ACTIVITY IN M. tuberculosis STRAINS WITH PHENOTYPIC SENSITIVITY AND RESISTANCE TO PYRAZINAMIDE
In order to detect the mechanisms of development of pyrazinamide resistance in M. tuberculosis, we carried out a complex analysis involving simultaneous determination of phenotypic sensitivity to pyrazinamide, pyrazinamidase activity, structures of genes encoding pyrazinamidase, pyrazinamide target and MIC. We demonstrated the key role of impaired pyrazinamidase activity due to mutations in the pncA gene. We described a wide spectrum of mutations in this gene and detected those, which preconditioned the borderline resistance to pyrazinamide. Mutations in the rpsA gene encoding the drug target did not affect the development of pyrazinamide resistance.