A multiple genome analysis of Mycobacterium tuberculosis reveals specific novel genes and mutations associated with pyrazinamide resistance
Type
DatasetAuthors
Sheen, PatriciaRequena, David
Gushiken, Eduardo
Gilman, Robert H.
Antiparra, Ricardo
Lucero, Bryan
Lizárraga, Pilar
Cieza, Basilio
Roncal, Elisa
Grandjean, Louis
Pain, Arnab
McNerney, Ruth
Clark, Taane G.
Moore, David
Zimic, Mirko
KAUST Department
Biological and Environmental Sciences and Engineering (BESE) DivisionBioscience Program
Pathogen Genomics Laboratory
Date
2017Permanent link to this record
http://hdl.handle.net/10754/663880Metadata
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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 68Â 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.Citation
Sheen, P., Requena, D., Gushiken, E., Gilman, R., Antiparra, R., Lucero, B., LizĂĄrraga, P., Cieza, B., Roncal, E., Grandjean, L., Arnab Pain, McNerney, R., Taane Clark, Moore, D., & Zimic, M. (2017). A multiple genome analysis of Mycobacterium tuberculosis reveals specific novel genes and mutations associated with pyrazinamide resistance. Figshare. https://doi.org/10.6084/M9.FIGSHARE.C.3902473.V1Publisher
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Is Supplement To:- [Article]
Sheen P, Requena D, Gushiken E, Gilman RH, Antiparra R, et al. (2017) A multiple genome analysis of Mycobacterium tuberculosis reveals specific novel genes and mutations associated with pyrazinamide resistance. BMC Genomics 18. Available: http://dx.doi.org/10.1186/s12864-017-4146-z.. DOI: 10.1186/s12864-017-4146-z HANDLE: 10754/625883
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