A multiple genome analysis of Mycobacterium tuberculosis reveals specific novel genes and mutations associated with pyrazinamide resistance.
BMC Genomics
; 18(1): 769, 2017 Oct 11.
Article
en En
| MEDLINE
| ID: mdl-29020922
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.Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Pirazinamida
/
Genómica
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Farmacorresistencia Bacteriana
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Genes Bacterianos
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Mutación
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Mycobacterium tuberculosis
Tipo de estudio:
Risk_factors_studies
Idioma:
En
Año:
2017
Tipo del documento:
Article