Format

Send to

Choose Destination
OMICS. 2017 Jul;21(7):413-425. doi: 10.1089/omi.2017.0070.

Whole Genome Sequencing of Mycobacterium tuberculosis Isolates From Extrapulmonary Sites.

Author information

1
1 Department of Medical Microbiology, PGIMER , Chandigarh, India .
2
2 Institute of Bioinformatics , International Technology Park, Bangalore, India .
3
3 School of Biotechnology, KIIT University , Bhubaneswar, India .
4
4 Manipal University , Manipal, India .
5
5 School of Biotechnology , Amrita Vishwa Vidyapeetham, Kollam, India .
6
6 Department of Internal Medicine, PGIMER, Chandigarh, India .
7
7 Department of Neurology, PGIMER, Chandigarh, India .
8
8 Department of Neurosurgery, PGIMER, Chandigarh, India .
9
9 Department of Orthopedics, PGIMER, Chandigarh, India .
10
10 YU-IOB Center for Systems Biology and Molecular Medicine , Mangalore, India .
11
11 McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine , Baltimore, Maryland.
12
12 Department of Biological Chemistry, Johns Hopkins University School of Medicine , Baltimore, Maryland.
13
13 Department of Pathology, Johns Hopkins University School of Medicine , Baltimore, Maryland.
14
14 Department of Oncology, Johns Hopkins University School of Medicine , Baltimore, Maryland.
15
15 NIMHANS-IOB Proteomics and Bioinformatics Laboratory, Neurobiology Research Centre, National Institute of Mental Health and Neurosciences , Bangalore, India .

Abstract

Tuberculosis (TB) remains one of the leading causes of morbidity and mortality worldwide. Extrapulmonary tuberculosis (EPTB) constitutes around 15-20% of TB cases in immunocompetent individuals. Extrapulmonary sites that are affected by TB include bones, lymph nodes, meningitis, pleura, and genitourinary tract. Whole genome sequencing has emerged as a powerful tool to map genetic diversity among Mycobacterium tuberculosis (MTB) isolates and identify the genomic signatures associated with drug resistance, pathogenesis, and disease transmission. Several pulmonary isolates of MTB have been sequenced over the years. However, availability of whole genome sequences of MTB isolates from extrapulmonary sites is limited. Some studies suggest that genetic variations in MTB might contribute to disease presentation in extrapulmonary sites. This can be addressed if whole genome sequence data from large number of extrapulmonary isolates becomes available. In this study, we have performed whole genome sequencing of five MTB clinical isolates derived from EPTB sites using next-generation sequencing platform. We identified 1434 nonsynonymous single nucleotide variations (SNVs), 143 insertions and 105 deletions. This includes 279 SNVs that were not reported before in publicly available datasets. We found several mutations that are known to confer resistance to drugs. All the five isolates belonged to East-African-Indian lineage (lineage 3). We identified 9 putative prophage DNA integrations and 14 predicted clustered regularly interspaced short palindromic repeats (CRISPR) in MTB genome. Our analysis indicates that more work is needed to map the genetic diversity of MTB. Whole genome sequencing in conjunction with comprehensive drug susceptibility testing can reveal clinically relevant mutations associated with drug resistance.

KEYWORDS:

coding DNA sequence; lineage; lymphadenitis; nonsynonymous; octal code

PMID:
28692415
DOI:
10.1089/omi.2017.0070
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Atypon
Loading ...
Support Center