毒素-抗毒素系统突变与耐药结核病全球传播之间的关系。

IF 3.4 3区 医学 Q2 INFECTIOUS DISEASES BMC Infectious Diseases Pub Date : 2024-11-05 DOI:10.1186/s12879-024-10142-4
Yameng Li, Yang Shao, Yifan Li, Xianglong Kong, Ningning Tao, Yawei Hou, Tingting Wang, Yingying Li, Yao Liu, Huaichen Li
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引用次数: 0

摘要

背景:耐多药结核病(MDR-TB)的出现对全球结核病控制工作构成了重大威胁。本研究旨在探讨毒素-抗毒素系统基因突变对结核分枝杆菌(M. tuberculosis)引起的耐多药结核病全球传播的影响:方法:对 13,518 例结核分枝杆菌分离株进行了全基因组测序。毒素-抗毒素系统的基因来自美国国家生物技术信息中心(NCBI)基因数据库。采用随机森林、梯度提升决策树和广义线性混合模型等技术来确定毒素-抗毒素系统相关基因中促进 MDR-TB 传播的突变位点:在所有分析的分离株中,有 4,066 株(30.08%)被确定为 MDR-TB 菌株。我们发现了特定基因突变与 MDR-TB 传播集群之间的重要关联,包括 Rv0298 (G213A)、Rv1959c (parE1, C88T)、Rv1960c (parD1, C134T)、Rv1991A (maze, G156A)、Rv2547 (vapB, C54G)、Rv2862A (vapB23, T2C) 和 Rv3385c (vapB46, G70A) 的突变。此外,还发现了一些与 MDR-TB 传播支系相关的基因突变,如 Rv1956(higA,G445T)、Rv1960c(parD1,C134T)和 Rv1962A(vapB35,G99A)。某些基因突变包括 vapB35 (G99A)、higA (G445T) 和 parD1 (C134T) 与跨区域传播支系相关:本研究强调了毒素-抗毒素系统中特定基因突变与 MDR-TB 全球传播之间的重要关联,为制定有针对性的干预措施以控制 MDR-TB 提供了宝贵的见解。
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Association between toxin-antitoxin system mutations and global transmission of MDR-TB.

Background: The emergence of Multidrug-Resistant Tuberculosis (MDR-TB) poses a significant threat to global tuberculosis control efforts. This study aimed to examine the influence of mutations in Toxin-Antitoxin system genes on the global transmission of MDR-TB caused by Mycobacterium tuberculosis (M. tuberculosis).

Methods: Whole-genome sequencing was conducted on 13,518 M. tuberculosis isolates. Genes of the Toxin-Antitoxin system were obtained from the National Center for Biotechnology Information (NCBI) Gene database. Techniques such as Random Forest, Gradient Boosting Decision Tree, and Generalized Linear Mixed Models were employed to identify mutation sites in Toxin-Antitoxin system-related genes that facilitated the transmission of MDR-TB.

Results: 4,066 (30.08%) were identified as MDR-TB strains of all analyzed isolates. We found significant associations between specific gene mutations and MDR-TB transmission clusters including mutations in Rv0298 (G213A), Rv1959c (parE1, C88T), Rv1960c (parD1, C134T), Rv1991A (maze, G156A), Rv2547 (vapB, C54G), Rv2862A (vapB23, T2C), and Rv3385c (vapB46, G70A). Additionally, several gene mutations associated with MDR-TB transmission clades such as Rv1956 (higA, G445T), Rv1960c (parD1, C134T), and Rv1962A (vapB35, G99A) were noted. Certain gene mutations including vapB35 (G99A), higA (G445T), and parD1 (C134T) correlated with cross-regional transmission clades.

Conclusion: This study highlights the significant association between specific gene mutations in the Toxin-Antitoxin system and the global transmission of MDR-TB, providing valuable insights for developing targeted interventions to control MDR-TB.

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来源期刊
BMC Infectious Diseases
BMC Infectious Diseases 医学-传染病学
CiteScore
6.50
自引率
0.00%
发文量
860
审稿时长
3.3 months
期刊介绍: BMC Infectious Diseases is an open access, peer-reviewed journal that considers articles on all aspects of the prevention, diagnosis and management of infectious and sexually transmitted diseases in humans, as well as related molecular genetics, pathophysiology, and epidemiology.
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