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

BMC Genomics

Research Article

Arnab Pain¹  Louis Grandjean²  Robert H. Gilman³  Ruth McNerney⁴  David Moore⁴  Taane G. Clark⁵  Bryan Lucero⁶  Basilio Cieza⁶  Patricia Sheen⁶  David Requena⁶  Ricardo Antiparra⁶  Elisa Roncal⁶  Eduardo Gushiken⁶  Pilar Lizárraga⁶  Mirko Zimic⁶ 

[1] Biological and Environmental Sciences and Engineering Division, King Abdullah University of Science & Technology, Thuwal, Kingdom of Saudi Arabia;Department of Infection, Immunology and Rheumatology, Institute of Child Health, University College London, 30 Guilford St, WC1N 1EH, London, UK;Department of International Health, Johns Hopkins Bloomberg School of Public Health, 615 North Wolfe St., Room 5515, 21205, Baltimore, MD, USA;Faculty of Infectious and Tropical Diseases, London School of Hygiene & Tropical Medicine, WC1E 7HT, London, UK;Faculty of Infectious and Tropical Diseases, London School of Hygiene & Tropical Medicine, WC1E 7HT, London, UK;Faculty of Epidemiology and Population Health, London School of Hygiene & Tropical Medicine, WC1E 7HT, London, UK;Laboratorio de Bioinformática y Biología Molecular. Laboratorios de Investigación y Desarrollo, Facultad de Ciencias y Filosofía, Universidad Peruana Cayetano Heredia, Av. Honorio Delgado 430, San Martín de Porras, 31, Lima, Peru;

关键词: Tuberculosis;    Pyrazinamide;    Resistance;    Genome;    Mutations;    MDR;    Metallochaperone;    Efflux pump;    Genes;    Drugs;   

DOI  :  10.1186/s12864-017-4146-z

 received in 2017-02-10, accepted in 2017-10-02,  发布年份 2017

来源: Springer

【 摘 要 】

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.

【 授权许可】

CC BY   
© The Author(s). 2017