Abstract
BackgroundTuberculosis (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.ResultsWe 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.ConclusionsThese 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.
Highlights
Tuberculosis (TB) is a major global health problem and drug resistance compromises the efforts to control this disease
After excluding genes linked to resistance to other drugs and pncA, we found a set of genes associated with PZA resistance
In this study we analyzed 68 M. tuberculosis complete genomes isolated from TB patients in Peru, and identified a set of novel mutations and genes significantly associated with PZA resistance in M. tuberculosis
Summary
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. Tuberculosis (TB) caused by the Mycobacterium tuberculosis bacilli is one of the most important global infectious diseases. While other first line anti-TB drugs affect fast growing metabolically active bacilli, pyrazinamide (PZA) is effective against non-replicating persistent. Sheen et al BMC Genomics (2017) 18:769 potential. This affects transport of nutrients [5], and interference of trans-translation by binding to the ribosomal protein RpsA [6] and competing with the tmRNA [7]
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