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. 2024 Nov 5;24(1):1250.
doi: 10.1186/s12879-024-10142-4.

Association between toxin-antitoxin system mutations and global transmission of MDR-TB

Yameng Li #  1   2 , Yang Shao #  1 , Yifan Li  3 , Xianglong Kong  4 , Ningning Tao  1 , Yawei Hou  5 , Tingting Wang  2 , Yingying Li  2 , Yao Liu  6 , Huaichen Li  7   8
Affiliations

Association between toxin-antitoxin system mutations and global transmission of MDR-TB

Yameng Li et al. BMC Infect Dis. .

Abstract

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.

Keywords: Gene mutations; Multidrug-resistant tuberculosis; Toxin-antitoxin system; Transmission.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
The distribution of M. tuberculosis strains in a specific region and the proportion of MDR strains
Fig. 2
Fig. 2
Correlation analysis of toxin-antitoxin system gene mutations and clade size of MDR-TB
Fig. 3
Fig. 3
SNPs in toxin-antitoxin system genes that confer to MDR isolates. Synonymous mutations were marked as dark blue stars, stop codons were represented by light blue stars, and missense mutations were indicated by red stars
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