Please use this identifier to cite or link to this item: https://doi.org/10.1038/s41598-018-23337-y
Title: Comparative whole-genome sequence analysis of Mycobacterium tuberculosis isolated from tuberculous meningitis and pulmonary tuberculosis patients
Authors: Faksri, K
Xia, E 
Ong, R.T.-H 
Tan, J.H 
Nonghanphithak, D
Makhao, N
Thamnongdee, N
Thanormchat, A
Phurattanakornkul, A
Rattanarangsee, S
Ratanajaraya, C
Suriyaphol, P
Prammananan, T
Teo, Y.-Y 
Chaiprasert, A
Keywords: bacterial protein
polyketide synthase
adult
comparative study
female
genetics
genotype
human
lung tuberculosis
male
microbiology
middle aged
Mycobacterium tuberculosis
phylogeny
single nucleotide polymorphism
tuberculous meningitis
whole genome sequencing
young adult
Adult
Bacterial Proteins
Female
Genotype
Humans
Male
Middle Aged
Mycobacterium tuberculosis
Phylogeny
Polyketide Synthases
Polymorphism, Single Nucleotide
Tuberculosis, Meningeal
Tuberculosis, Pulmonary
Whole Genome Sequencing
Young Adult
Issue Date: 2018
Citation: Faksri, K, Xia, E, Ong, R.T.-H, Tan, J.H, Nonghanphithak, D, Makhao, N, Thamnongdee, N, Thanormchat, A, Phurattanakornkul, A, Rattanarangsee, S, Ratanajaraya, C, Suriyaphol, P, Prammananan, T, Teo, Y.-Y, Chaiprasert, A (2018). Comparative whole-genome sequence analysis of Mycobacterium tuberculosis isolated from tuberculous meningitis and pulmonary tuberculosis patients. Scientific Reports 8 (1) : 23337. ScholarBank@NUS Repository. https://doi.org/10.1038/s41598-018-23337-y
Abstract: 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. © 2018 The Author(s).
Source Title: Scientific Reports
URI: https://scholarbank.nus.edu.sg/handle/10635/175027
ISSN: 20452322
DOI: 10.1038/s41598-018-23337-y
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