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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.    Electronic supplementary material  The online version of this article (10.1186/s12864-017-4146-z) contains supplementary material, which is available to authorized users.

A multiple genome analysis of Mycobacterium tuberculosis reveals specific novel genes and mutations associated with pyrazinamide resistance