ORIGINAL RESEARCH article
Front. Cell. Infect. Microbiol.
Sec. Bacteria and Host
Volume 15 - 2025 | doi: 10.3389/fcimb.2025.1573643
Type Ⅶ Secretion System Gene Mutations Driving Global Mycobacterium Tuberculosis Transmission Revealed by Whole Genomic Sequence
Provisionally accepted
- 1Shandong University of Traditional Chinese Medicine, Jinan, Shandong Province, China
- 2Shandong Province Third Hospital, Jinan, Shandong Province, China
- 3Jining Medical University, Jining, Shandong, China
- 4People’s Hospital of Huaiyin Jinan, Jinan 250000, China., Jinan, Shandong Province, China
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Introduction: Pathogenic mycobacteria are able to transfer virulence factors across their complex cell wall using a type VII secretion system (T7SS)/early secreted antigenic target-6 of the kDa secretion system (ESX). Since the discovery of ESX loci during the Mycobacterium tuberculosisM. tuberculosis H37Rv genome project, extensive research in areas such as structural biology, cell biology, and evolutionary analysis has improved our understanding of the role of these systems. However, regulatory mechanisms for ESX in Mycobacterium tuberculosisM.tb remain elusive. Despite extensive research, the effects of ESX gene mutations on the dynamics of Mycobacterium tuberculosisM.tb transmission are not well understood. In this study, we investigated the role of ESX mutations in TB transmission, assessing their risk and characteristics. We analyzed 13582 whole genome sequences of Mycobacterium tuberculosis isolates, of which 6130 (45.13%) were clustered strains. Initially, Boruta algorithm was used to pinpoint SNPs that were significant for TB transmission. These SNPs were then subjected to univariate and multivariate logistic regression analysis to determine the significance of each SNP. The intersection of these two independent methods was recognized as the optimal set of risk mutations for TB transmission. Specifically, we identified one risk mutation (espA(Rv3616c, 4055801)) in L1, four risk mutations (espK( Rv3879c, 4357597), esxU(Rv3445c, 3863138), esxO(Rv2346c, 2626018), and esxW(Rv3620c, 4060588)) in L2, and four risk mutations (eccE1(Rv3882c, 4362807), espE(Rv3864, 4340330), espA(Rv3616c, 4055993), and eccC5(Rv1783, 2019942)) in L4. These risk mutations were significantly associated with clustering, potentially increasing TB transmission.
Keywords: Mycobacterium tuberculosis, Mutation, ESX, transmission, phylogenetic analysis
Received: 18 Feb 2025; Accepted: 14 May 2025.
Copyright: © 2025 Yang, Hu, Sun, Wang, Xie 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:
Xianjin Xie, Shandong Province Third Hospital, Jinan, Shandong Province, China
Tingting Wang, Shandong Province Third Hospital, Jinan, Shandong Province, China
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