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ORIGINAL RESEARCH article

Front. Microbiol.
Sec. Infectious Agents and Disease
Volume 15 - 2024 | doi: 10.3389/fmicb.2024.1398886
This article is part of the Research Topic Tuberculosis diagnosis, drug resistance, and drug target discovery View all 16 articles

Toxin-Antitoxin system gene mutations driving Mycobacterium tuberculosis transmission revealed by Whole genome sequencing

Provisionally accepted
Yawei Hou Yawei Hou 1YiFan Li YiFan Li 2Ningning Tao Ningning Tao 3Xianglong Kong Xianglong Kong 4Yameng Li Yameng Li 5Yao Liu Yao Liu 3*huaichen li huaichen li 3*zhenguo wang zhenguo wang 1*
  • 1 Institute of Chinese Medical Literature and Culture, Shandong University of Traditional Chinese Medicine, Jinan, Shandong Province, China
  • 2 The Third Affiliated Hospital of Shandong First Medical University, Jinan, Shandong Province, China
  • 3 Department of Respiratory and Critical Care Medicine, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China
  • 4 Shandong Artificial Intelligence Institute, Qilu University of Technology, Jinan, Shandong Province, China
  • 5 The First Clinical Medical College, Shandong University of Traditional Chinese Medicine,, Jinan, Shandong Province, China

The final, formatted version of the article will be published soon.

    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.To investigate the influence of gene mutations in the toxin-antitoxin system on M. tuberculosis transmission dynamics.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.A total of 13,518 M. tuberculosis isolates were analyzed, with 42.29%(n=5717) 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.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.

    Keywords: toxin-antitoxin system, Mycobacterium tuberculosis, transmission, whole genome sequencing, Single nucleotide polymorphisms

    Received: 11 Mar 2024; Accepted: 22 Jul 2024.

    Copyright: © 2024 Hou, Li, Tao, Kong, Li, Liu, li and wang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence:
    Yao Liu, Department of Respiratory and Critical Care Medicine, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China
    huaichen li, Department of Respiratory and Critical Care Medicine, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China
    zhenguo wang, Institute of Chinese Medical Literature and Culture, Shandong University of Traditional Chinese Medicine, Jinan, Shandong Province, China

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