2024-03-28T16:27:15Zhttp://digital.csic.es/dspace-oai/requestoai:digital.csic.es:10261/2145362021-12-27T16:47:18Zcom_10261_109com_10261_1col_10261_362
DIGITAL.CSIC
author
Liu, Qingyun
author
Wei, Jianhao
author
Li, Yawei
author
Wang, Mei
author
Su, Jun
author
Lu, Yonghui
author
López, Mariana G.
author
Qian, Xueqin
author
Zhu, Zhaoqin
author
Wang, Haiying
author
Gan, Mingyun
author
Jiang , Qi
author
Fu, Yun-Xin
author
Takiff, Howard E.
author
Comas, Iñaki
author
Li, Feng
author
Lu, Xuemei
author
Fortune, Sarah M.
author
Gao, Qian
funder
National Natural Science Foundation of China
funder
Ministry of Science and Technology of the People's Republic of China
funder
European Research Council
funder
Chinese Academy of Sciences
funder
National Institutes of Health (US)
orcid
Comas, Iñaki [0000-0001-5504-9408]
2020-06-16T11:22:01Z
2020-06-16T11:22:01Z
2020-05-29
Science advances 6(22):eaba4901 (2020)
http://hdl.handle.net/10261/214536
10.1126/sciadv.aba4901
2375-2548
http://dx.doi.org/10.13039/100000002http://dx.doi.org/10.13039/501100001809http://dx.doi.org/10.13039/501100000781http://dx.doi.org/10.13039/501100002367http://dx.doi.org/10.13039/501100002855
32524000
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-naïve 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.
eng
openAccess
Mycobacterium tuberculosis clinical isolates carry mutational signatures of host immune environments
artículo
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URL
https://digital.csic.es/bitstream/10261/214536/1/2020%20Sci%20Adv%206-eaba4901.pdf
File
MD5
908217da0974c2ce1392db63fd6724ef
994847
application/pdf
2020 Sci Adv 6-eaba4901.pdf