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使用全基因组测序估计复发性结核病例中结核分枝杆菌的突变率。

Estimation of the mutation rate of Mycobacterium tuberculosis in cases with recurrent tuberculosis using whole genome sequencing.

机构信息

Instituto Aragonés de Ciencias de la Salud, C/de San Juan Bosco, 13, 50009, Zaragoza, Spain.

Unidad de Biocomputación, Instituto Aragonés de Ciencias de la Salud, C/de San Juan Bosco, 13, 50009, Zaragoza, Spain.

出版信息

Sci Rep. 2022 Oct 6;12(1):16728. doi: 10.1038/s41598-022-21144-0.

DOI:10.1038/s41598-022-21144-0
PMID:36202945
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9537313/
Abstract

The study of tuberculosis latency is problematic due to the difficulty of isolating the bacteria in the dormancy state. Despite this, several in vivo approaches have been taken to mimic the latency process. Our group has studied the evolution of the bacteria in 18 cases of recurrent tuberculosis. We found that HIV positive patients develop recurrent tuberculosis earlier, generally in the first two years (p value = 0.041). The genome of the 36 Mycobacterium tuberculosis paired isolates (first and relapsed isolates) showed that none of the SNPs found within each pair was observed more than once, indicating that they were not directly related to the recurrence process. Moreover, some IS6110 movements were found in the paired isolates, indicating the presence of different clones within the patient. Finally, our results suggest that the mutation rate remains constant during all the period as no correlation was found between the number of SNPs and the time to relapse.

摘要

由于难以分离休眠状态下的细菌,潜伏性结核病的研究存在问题。尽管如此,还是有几种体内方法被用于模拟潜伏过程。我们的小组研究了 18 例复发性结核病中细菌的进化。我们发现 HIV 阳性患者更早地出现复发性结核病,通常在头两年(p 值=0.041)。36 对结核分枝杆菌配对分离株(初次和复发分离株)的基因组显示,每对中发现的 SNPs 都没有一次以上的重复,这表明它们与复发过程没有直接关系。此外,在配对分离株中发现了一些 IS6110 移动,表明患者体内存在不同的克隆。最后,我们的结果表明,突变率在整个过程中保持不变,因为没有发现 SNP 数量与复发时间之间存在相关性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f043/9537313/f1a83559233f/41598_2022_21144_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f043/9537313/f961165fc14c/41598_2022_21144_Fig1_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f043/9537313/f1a83559233f/41598_2022_21144_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f043/9537313/f961165fc14c/41598_2022_21144_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f043/9537313/11a984f33846/41598_2022_21144_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f043/9537313/463d12f071c8/41598_2022_21144_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f043/9537313/adacebc37ed9/41598_2022_21144_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f043/9537313/f1a83559233f/41598_2022_21144_Fig5_HTML.jpg

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