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

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

Publication date: Nov 05, 2024

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). 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. 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. 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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Concepts Keywords
Biotechnology Gene mutations
Database Multidrug-resistant tuberculosis
Rv2547 Toxin-antitoxin system
Tuberculosis Transmission
Valuable

Semantics

Type Source Name
disease IDO toxin
disease MESH Multidrug-Resistant Tuberculosis
disease MESH tuberculosis
pathway KEGG Tuberculosis
drug DRUGBANK Flunarizine
pathway REACTOME Reproduction
disease MESH Infectious Diseases
drug DRUGBANK Coenzyme M
drug DRUGBANK Isoniazid
drug DRUGBANK Rifampicin
drug DRUGBANK Trestolone
disease IDO replication
disease IDO production
disease IDO bacteria
disease IDO host
disease IDO virulence
disease IDO drug susceptibility
drug DRUGBANK Tretamine
disease IDO quality
drug DRUGBANK Methionine
drug DRUGBANK Methylergometrine
drug DRUGBANK Ademetionine
drug DRUGBANK Nonoxynol-9
drug DRUGBANK Spinosad
disease IDO susceptibility
disease MESH mutation frequency
drug DRUGBANK Esomeprazole
drug DRUGBANK Isoxaflutole
disease IDO protein
disease IDO process
disease IDO cell
disease MESH death
disease MESH infection
disease MESH Comas
disease MESH RFLP
disease IDO algorithm
drug DRUGBANK Latrunculin A
drug DRUGBANK Vorinostat

Original Article

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