AI Article Synopsis
- Tuberculosis (TB) is a significant global health issue, with drug resistance, especially to Pyrazinamide (PZA), complicating treatment efforts.
- Researchers analyzed 68 M. tuberculosis strains from TB patients in Peru, identifying no clear genetic clustering but discovering mutations in the pncA gene and other novel genes linked to PZA resistance.
- These findings indicate that PZA resistance may involve multiple mechanisms, suggesting that the drug targets several biological pathways instead of just one.
Article Abstract
Background: Tuberculosis (TB) is a major global health problem and drug resistance compromises the efforts to control this disease. Pyrazinamide (PZA) is an important drug used in both first and second line treatment regimes. However, its complete mechanism of action and resistance remains unclear.
Results: We genotyped and sequenced the complete genomes of 68 M. tuberculosis strains isolated from unrelated TB patients in Peru. No clustering pattern of the strains was verified based on spoligotyping. We analyzed the association between PZA resistance with non-synonymous mutations and specific genes. We found mutations in pncA and novel genes significantly associated with PZA resistance in strains without pncA mutations. These included genes related to transportation of metal ions, pH regulation and immune system evasion.
Conclusions: These results suggest potential alternate mechanisms of PZA resistance that have not been found in other populations, supporting that the antibacterial activity of PZA may hit multiple targets.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5637355 | PMC |
| http://dx.doi.org/10.1186/s12864-017-4146-z | DOI Listing |
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