| Autor: |
Hang NTL; NCGM-BMH Medical Collaboration Center, Hanoi, Vietnam., Hijikata M; Department of Pathophysiology and Host Defense, The Research Institute of Tuberculosis, JATA, Tokyo, Japan., Maeda S; Faculty of Pharmaceutical Sciences, Hokkaido University of Science, Hokkaido, Japan., Thuong PH; Hanoi Lung Hospital, Hanoi, Vietnam., Ohashi J; Department of Biological Sciences, Graduate School of Science, The University of Tokyo, Tokyo, Japan., Van Huan H; Hanoi Lung Hospital, Hanoi, Vietnam., Hoang NP; Department of Microbiology, Hanoi Lung Hospital, Hanoi, Vietnam., Miyabayashi A; Department of Pathophysiology and Host Defense, The Research Institute of Tuberculosis, JATA, Tokyo, Japan., Cuong VC; Hanoi Department of Health, Hanoi, Vietnam., Seto S; Department of Pathophysiology and Host Defense, The Research Institute of Tuberculosis, JATA, Tokyo, Japan., Van Hung N; Department of Microbiology, National Lung Hospital, Hanoi, Vietnam., Keicho N; The Research Institute of Tuberculosis JATA, Tokyo, Japan. nkeicho-tky@umin.ac.jp.; National Center for Global Health and Medicine, Tokyo, Japan. nkeicho-tky@umin.ac.jp. |
| Abstrakt: |
Drug-resistant tuberculosis (TB) is a serious global problem, and pathogen factors involved in the transmission of isoniazid (INH)-resistant TB have not been fully investigated. We performed whole genome sequencing of 332 clinical Mycobacterium tuberculosis (Mtb) isolates collected from patients newly diagnosed with smear-positive pulmonary TB in Hanoi, Vietnam. Using a bacterial genome-wide approach based on linear mixed models, we investigated the associations between 31-bp k-mers and clustered strains harboring katG-S315T, a major INH-resistance mutation in the present cohort and in the second panel previously published in South Africa. Five statistically significant genes, namely, PPE18/19, gid, emrB, Rv1588c, and pncA, were shared by the two panels. We further identified variants of the genes responsible for these k-mers, which are relevant to the spread of INH-resistant strains. Phylogenetic convergence test showed that variants relevant to PPE46/47-like chimeric genes were significantly associated with the same phenotype in Hanoi. The associations were further confirmed after adjustment for the confounders. These findings suggest that genomic variations of the pathogen facilitate the expansion of INH-resistance TB, at least in part, and our study provides a new insight into the mechanisms by which drug-resistant Mtb maintains fitness and spreads in Asia and Africa. |
