The antituberculosis drug pyrazinamide (PZA) needs to be converted into pyrazinoic acid (POA) by the bacterial pyrazinamidase (PZase) in order to show bactericidal activity against is naturally resistant to PZA. To investigate whether this natural resistance to PZA is due to inability of the PZase to convert PZA to bactericidal POA, the PZase gene () was cloned by using the gene as a probe. Sequence analysis showed that the gene is 561 bp long, encoding a protein with a predicted size of about 19-8 kDa; but Western blotting showed that the PZase migrated as a 24 kDa band when expressed in BCG and Sequence comparison revealed that PZase has 67.7% and 32.8% amino acid identity with the corresponding enzymes from and respectively. Southern blot analysis with the gene as a probe showed that and have close homologues, whereas and did not give significant hybridization signals. Transformation with the gene conferred PZA susceptibility to PZA-resistant complex organisms, indicating that the nonsusceptibility of to PZA is not due to an ineffective PZase enzyme, but appears to be related to other factors such as transport of POA.


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