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Title: Comparative whole-genome sequence analysis of Mycobacterium tuberculosis isolated from tuberculous meningitis and pulmonary tuberculosis patients
Authors: Kiatichai Faksri
Eryu Xia
Rick Twee Hee Ong
Jun Hao Tan
Ditthawat Nonghanphithak
Nampueng Makhao
Nongnard Thamnongdee
Arirat Thanormchat
Arisa Phurattanakornkul
Somcharn Rattanarangsee
Chate Ratanajaraya
Prapat Suriyaphol
Therdsak Prammananan
Yik Ying Teo
Angkana Chaiprasert
NUS Graduate School for Integrative Sciences and Engineering
A-Star, Genome Institute of Singapore
Faculty of Medicine, Khon Kaen University
Khon Kaen University
National University of Singapore
Thailand National Center for Genetic Engineering and Biotechnology
Faculty of Medicine, Siriraj Hospital, Mahidol University
Keywords: Multidisciplinary
Issue Date: 1-Dec-2018
Citation: Scientific Reports. Vol.8, No.1 (2018)
Abstract: © 2018 The Author(s). Tuberculous meningitis (TBM) is a severe form of tuberculosis with a high mortality rate. The factors associated with TBM pathogenesis are still unclear. Using comparative whole-genome sequence analysis we compared Mycobacterium tuberculosis (Mtb) isolates from cerebrospinal fluid of TBM cases (n = 73) with those from sputum of pulmonary tuberculosis (PulTB) patients (n = 220) from Thailand. The aim of this study was to seek genetic variants of Mtb associated with TBM. Regardless of Mtb lineage, we found 242 variants that were common to all TBM isolates. Among these variants, 28 were missense SNPs occurring mainly in the pks genes (involving polyketide synthesis) and the PE/PPE gene. Six lineage-independent SNPs were commonly found in TBM isolates, two of which were missense SNPs in Rv0532 (PE-PGRS6). Structural variant analysis revealed that PulTB isolates had 14 genomic regions containing 2-3-fold greater read depth, indicating higher copy number variants and half of these genes belonged to the PE/PPE gene family. Phylogenetic analysis revealed only two small clusters of TBM clonal isolates without support from epidemiological data. This study reported genetic variants of Mtb commonly found in TBM patients compared to PulTB patients. Variants associated with TBM disease warrant further investigation.
ISSN: 20452322
Appears in Collections:Scopus 2018

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