Iron-related gene mutations driving global Mycobacterium tuberculosis transmission revealed by whole-genome sequencing
Yameng Li,
Yifan Li,
Yao Liu,
Xianglong Kong,
Ningning Tao,
Yawei Hou,
Tingting Wang,
Qilin Han,
Yuzhen Zhang,
Fei Long,
Huaichen Li
Affiliations
Yameng Li
Clinical Department of Integrated Traditional Chinese and Western Medicine , The First Clinical Medical College of Shandong University of Traditional Chinese Medicine
Yifan Li
Department of Pulmonary and Critical Care Medicine, The Third Affiliated Hospital of Shandong First Medical University (Affiliated Hospital of Shandong Academy of Medical Sciences)
Yao Liu
Department of Pulmonary and Critical Care Medicine, Shandong Provincial Hospital Affiliated to Shandong University, Shandong Provincial Hospital Affiliated to Shandong First Medical University
Xianglong Kong
Artificial Intelligence Institute, Qilu University of Technology (Shandong Academy of Sciences)
Ningning Tao
Department of Pulmonary and Critical Care Medicine, Shandong Provincial Hospital Affiliated to Shandong University, Shandong Provincial Hospital Affiliated to Shandong First Medical University
Yawei Hou
Institute of Chinese Medical Literature and Culture of Shandong University of Traditional Chinese Medicine
Tingting Wang
Clinical Department of Integrated Traditional Chinese and Western Medicine , The First Clinical Medical College of Shandong University of Traditional Chinese Medicine
Qilin Han
Shandong First Medical University & Shandong Academy of Medical Sciences
Yuzhen Zhang
Shandong First Medical University & Shandong Academy of Medical Sciences
Fei Long
Department of Pulmonary and Critical Care Medicine, The Third Affiliated Hospital of Shandong First Medical University (Affiliated Hospital of Shandong Academy of Medical Sciences)
Huaichen Li
Clinical Department of Integrated Traditional Chinese and Western Medicine , The First Clinical Medical College of Shandong University of Traditional Chinese Medicine
Abstract Background Iron plays a crucial role in the growth of Mycobacterium tuberculosis (M. tuberculosis). However, the precise regulatory mechanism governing this system requires further elucidation. Additionally, limited studies have examined the impact of gene mutations related to iron on the transmission of M. tuberculosis globally. This research aims to investigate the correlation between mutations in iron-related genes and the worldwide transmission of M. tuberculosis. Results A total of 13,532 isolates of M. tuberculosis were included in this study. Among them, 6,104 (45.11%) were identified as genomic clustered isolates, while 8,395 (62.04%) were classified as genomic clade isolates. Our results showed that a total of 12 single nucleotide polymorphisms (SNPs) showed a positive correlation with clustering, such as Rv1469 (ctpD, C758T), Rv3703c (etgB, G1122T), and Rv3743c (ctpJ, G676C). Additionally, seven SNPs, including Rv0104 (T167G, T478G), Rv0211 (pckA, A302C), Rv0283 (eccB3, C423T), Rv1436 (gap, G654T), ctpD C758T, and etgB C578A, demonstrated a positive correlation with transmission clades across different countries. Notably, our findings highlighted the positive association of Rv0104 T167G, pckA A302C, eccB3 C423T, ctpD C758T, and etgB C578A with transmission clades across diverse regions. Furthermore, our analysis identified 78 SNPs that exhibited significant associations with clade size. Conclusions Our study reveals the link between iron-related gene SNPs and M. tuberculosis transmission, offering insights into crucial factors influencing the pathogenicity of the disease. This research holds promise for targeted strategies in prevention and treatment, advancing research and interventions in this field.
