Mycobacterium tuberculosis clinical isolates carry mutational signatures of host immune environments
Por:
Liu Q, Wei J, Li Y, Wang M, Su J, Lu Y, López MG, Qian X, Zhu Z, Wang H, Gan M, Jiang Q, Fu YX, Takiff HE, Comas I, Li F, Lu X, Fortune SM and Gao Q
Publicada:
1 may 2020
Ahead of Print:
29 may 2020
Categoría:
Multidisciplinary
Resumen:
Mycobacterium tuberculosis (Mtb) infection results in a spectrum of clinical and histopathologic manifestations. It has been proposed that the environmental and immune pressures associated with different contexts of infection have different consequences for the associated bacterial populations, affecting drug susceptibility and the emergence of resistance. However, there is little concrete evidence for this model. We prospectively collected sputum samples from 18 newly diagnosed and treatment-naive patients with tuberculosis and sequenced 795 colony-derived Mtb isolates. Mutant accumulation rates varied considerably between different bacilli isolated from the same individual, and where high rates of mutation were observed, the mutational spectrum was consistent with reactive oxygen species-induced mutagenesis. Elevated bacterial mutation rates were identified in isolates from HIV-negative but not HIV-positive individuals, suggesting that they were immune-driven. These results support the model that mutagenesis of Mtb in vivo is modulated by the host environment, which could drive the emergence of variants associated with drug resistance in a host-dependent manner.
Filiaciones:
Liu Q:
Shanghai Public Health Clinical Center, Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), Shanghai Medical College and School of Basic Medical Sciences, Fudan University, Shanghai, China
Department of Immunology and Infectious Diseases, Harvard T. H. Chan School of Public Health, Boston, MA 02115, USA
Wei J:
Shanghai Public Health Clinical Center, Fudan University, Shanghai, China
Li Y:
CAS Key Laboratory of Genomic and Precision Medicine, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101, China
University of Chinese Academy of Sciences, Beijing 100049, China
Wang M:
Shanghai Public Health Clinical Center, Fudan University, Shanghai, China
Su J:
Shanghai Public Health Clinical Center, Fudan University, Shanghai, China
Lu Y:
Shanghai Public Health Clinical Center, Fudan University, Shanghai, China
López MG:
Tuberculosis Genomic Unit, Instituto de Biomedicina de Valencia (IBV-CSIC), Valencia, Spain
Qian X:
Shanghai Public Health Clinical Center, Fudan University, Shanghai, China
Zhu Z:
Shanghai Public Health Clinical Center, Fudan University, Shanghai, China
Wang H:
Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China
Gan M:
Molecular Medical Center, Children's Hospital of Fudan University, Shanghai, China
Jiang Q:
Shanghai Public Health Clinical Center, Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), Shanghai Medical College and School of Basic Medical Sciences, Fudan University, Shanghai, China
Shenzhen Center for Chronic Disease Control, Shenzhen, China
Fu YX:
Department of Biostatistics and Human Genetics Center, University of Texas Health Science Center at Houston, Houston, TX 77030, USA
Takiff HE:
Integrated Mycobacterial Pathogenomics Unit, Institut Pasteur, Paris, France
Nanshan Center for Chronic Disease Control, Shenzhen, China
:
Tuberculosis Genomic Unit, Instituto de Biomedicina de Valencia (IBV-CSIC), Valencia, Spain
CIBER in Epidemiology and Public Health (CIBERESP), Madrid, Spain
Li F:
Shanghai Public Health Clinical Center, Fudan University, Shanghai, China
Lu X:
State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, China
CAS Center for Excellence in Animal Evolution and Genetics, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, 650223, China
Fortune SM:
Department of Immunology and Infectious Diseases, Harvard T. H. Chan School of Public Health, Boston, MA 02115, USA
Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA
Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA
Gao Q:
Shanghai Public Health Clinical Center, Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), Shanghai Medical College and School of Basic Medical Sciences, Fudan University, Shanghai, China
Shenzhen Center for Chronic Disease Control, Shenzhen, China
gold, Green Published
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