期刊
BMC GENOMICS
卷 18, 期 -, 页码 -出版社
BMC
DOI: 10.1186/s12864-017-4146-z
关键词
Tuberculosis; Pyrazinamide; Resistance; Genome; Mutations; MDR; Metallochaperone; Efflux pump; Genes; Drugs
资金
- Wellcome Trust [099805/Z/12/Z]
- charity IFHAD: Innovation For Health And Development
- DFID-CSCF
- Joint Global Health Trials consortium (MRC, DFID & Wellcome Trust)
- Imperial College Biomedical Research Centre
- National Institute of Allergy and Infectious Diseases, National Institutes of Health US [1R01TW008669-01]
- Loreal UNESCO
- TWAS
- Grand Challenge Canada
- MRC UK [MR/K000551/1, MR/M01360X/1, MR/N010469/1, MC_PC_15103]
- KAUST
- Wellcome Trust [099805/Z/12/Z] Funding Source: Wellcome Trust
- MRC [MR/N010469/1, MR/K007467/1] Funding Source: UKRI
- Medical Research Council [MR/N010469/1, MR/K007467/1] Funding Source: researchfish
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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