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

Autor: Li Y; Department of Respiratory and Critical Care Medicine, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, 250021, Shandong, China.; College of the First Clinical Medical, Shandong University of Traditional Chinese Medicine, Jinan, 250355, Shandong, China., Shao Y; Department of Respiratory and Critical Care Medicine, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, 250021, Shandong, China., Li Y; Department of Respiratory and Critical Care Medicine, The Third Affiliated Hospital of Shandong First Medical University (Affiliated Hospital of Shandong Academy of Medical Sciences), Jinan, 250031, Shandong, China., Kong X; Artificial Intelligence Institute, Qilu University of Technology (Shandong Academy of Sciences), Jinan, 250011, Shandong, China., Tao N; Department of Respiratory and Critical Care Medicine, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, 250021, Shandong, China., Hou Y; Institute of Chinese Medical Literature and Culture, Shandong University of Traditional Chinese Medicine, Jinan, 250355, Shandong, China., Wang T; College of the First Clinical Medical, Shandong University of Traditional Chinese Medicine, Jinan, 250355, Shandong, China., Li Y; College of the First Clinical Medical, Shandong University of Traditional Chinese Medicine, Jinan, 250355, Shandong, China., Liu Y; Department of Respiratory and Critical Care Medicine, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, 250021, Shandong, China. doctorliu@126.com., Li H; Department of Respiratory and Critical Care Medicine, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, 250021, Shandong, China. lihuaichen@163.com.; College of the First Clinical Medical, Shandong University of Traditional Chinese Medicine, Jinan, 250355, Shandong, China. lihuaichen@163.com.
Jazyk: angličtina
Zdroj: BMC infectious diseases [BMC Infect Dis] 2024 Nov 05; Vol. 24 (1), pp. 1250. Date of Electronic Publication: 2024 Nov 05.
DOI: 10.1186/s12879-024-10142-4
Abstrakt: 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.
(© 2024. The Author(s).)
Databáze: MEDLINE
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