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Mycobacterium tuberculosis clinical isolates carry mutational signatures of host immune environments

AuthorsLiu, Qingyun; Wei, Jianhao; Li, Yawei; Wang, Mei; Su, Jun; Lu, Yonghui; López, Mariana G. ; Qian, Xueqin; Zhu, Zhaoqin; Wang, Haiying; Gan, Mingyun; Jiang , Qi; Fu, Yun-Xin; Takiff, Howard E.; Comas, Iñaki ; Li, Feng; Lu, Xuemei; Fortune, Sarah M.; Gao, Qian
Issue Date29-May-2020
PublisherAmerican Association for the Advancement of Science
CitationScience advances 6(22):eaba4901 (2020)
AbstractMycobacterium 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.
Description9 páginas, 4 figuras. All data needed to evaluate the conclusions in the paper are present in the paper and/or the Supplementary Materials. Additional data related to this paper may be requested from the authors. Sequencing reads have been submitted to the European Nucleotide Archive (EMBL-EBI) under study accession PRJEB34582 and PRJEB34609. The analysis scripts used in this study are available online at GitHub (https://github.com/StopTB/Single_Colony_Project).
Publisher version (URL)http://dx.doi.org/10.1126/sciadv.aba4901
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