■毒素-抗毒素(TA)系统在结核分枝杆菌的毒力和致病性中起着至关重要的作用(M.结核病)。然而,对于结核分枝杆菌的调控机制和基因突变对其传播的影响仍然知之甚少.
■研究毒素-抗毒素系统中基因突变对结核分枝杆菌传播动力学的影响。
■我们对所分析的结核分枝杆菌菌株进行了全基因组测序。从国家生物技术信息中心(NCBI)基因数据库获得与毒素-抗毒素系统相关的基因。通过使用随机森林鉴定与基因内增强传播相关的突变,梯度增强决策树,和广义线性混合模型。
■共分析了13,518株结核分枝杆菌,42.29%(n=5,717)被发现是基因组簇的一部分。谱系4占分离株的大多数(n=6488,48%),其次是谱系2(n=5133,37.97%)。23个单核苷酸多态性(SNPs)与聚类呈正相关,包括vapB1G34A,vapB24A76C,vapB2T171C,mazF2C85T,mazE2G104A,vapB31T112C,relBT226A,vapB11C54T,mazE5T344C,vapB14A29G,parE1(C103T,C88T),和parD1C134T。六个SNP,包括vapB6A29C,vapB31T112C,parD1C134T,vapB37G205C,Rv2653cA80C,和vapB22C167T,与不同国家的传播分支有关。值得注意的是,我们的发现强调了vapB6A29C的正相关,vapB31T112C,parD1C134T,vapB37G205C,vapB19C188T,和Rv2653cA80C,具有跨不同地区的传输分支。此外,我们的分析确定了32个与进化枝大小显著相关的SNP.
■我们的研究提出了与毒素-抗毒素系统相关的基因突变与结核分枝杆菌的传播动力学之间的潜在关联。然而,重要的是要承认我们研究中存在混杂因素和局限性.需要进一步的研究来建立因果关系并评估这些突变的功能意义。这些发现为未来的调查和制定旨在控制结核病传播的策略奠定了基础。
UNASSIGNED: The toxin-antitoxin (TA) system plays a vital role in the virulence and pathogenicity of Mycobacterium tuberculosis (M. tuberculosis). However, the regulatory mechanisms and the impact of gene mutations on M. tuberculosis transmission remain poorly understood.
UNASSIGNED: To investigate the influence of gene mutations in the toxin-antitoxin system on M. tuberculosis transmission dynamics.
UNASSIGNED: We performed whole-genome sequencing on the analyzed strains of M. tuberculosis. The genes associated with the toxin-antitoxin system were obtained from the National Center for Biotechnology Information (NCBI) Gene database. Mutations correlating with enhanced transmission within the genes were identified by using random forest, gradient boosting decision tree, and generalized linear mixed models.
UNASSIGNED: A total of 13,518 M. tuberculosis isolates were analyzed, with 42.29% (n = 5,717) found to be part of genomic clusters. Lineage 4 accounted for the majority of isolates (n = 6488, 48%), followed by lineage 2 (n = 5133, 37.97%). 23 single nucleotide polymorphisms (SNPs) showed a positive correlation with clustering, including vapB1 G34A, vapB24 A76C, vapB2 T171C, mazF2 C85T, mazE2 G104A, vapB31 T112C, relB T226A, vapB11 C54T, mazE5 T344C, vapB14 A29G, parE1 (C103T, C88T), and parD1 C134T. Six SNPs, including vapB6 A29C, vapB31 T112C, parD1 C134T, vapB37 G205C, Rv2653c A80C, and vapB22 C167T, were associated with transmission clades across different countries. Notably, our findings highlighted the positive association of vapB6 A29C, vapB31 T112C, parD1 C134T, vapB37 G205C, vapB19 C188T, and Rv2653c A80C with transmission clades across diverse regions. Furthermore, our analysis identified 32 SNPs that exhibited significant associations with clade size.
UNASSIGNED: Our study presents potential associations between mutations in genes related to the toxin-antitoxin system and the transmission dynamics of M. tuberculosis. However, it is important to acknowledge the presence of confounding factors and limitations in our study. Further research is required to establish causation and assess the functional significance of these mutations. These findings provide a foundation for future investigations and the formulation of strategies aimed at controlling TB transmission.