Whole Genome Sequencing of Mycobacterium tuberculosis Isolates from Extrapulmonary Sites

Kusum Sharma, Renu Verma, Jayshree Advani, Oishi Chatterjee, Hitendra S. Solanki, Aman Sharma, Subhash Varma, Manish Modi, Pallab Ray, Kanchan K. Mukherjee, Megha Sharma, Mandeed Singh Dhillion, Mrutyunjay Suar, Aditi Chatterjee, Akhilesh Pandey, Thottethodi Subrahmanya Keshava Prasad, Harsha Gowda

Research output: Contribution to journalArticle

5 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)413-425
Number of pages13
JournalOMICS A Journal of Integrative Biology
Volume21
Issue number7
DOIs
StatePublished - Jul 1 2017
Externally publishedYes

Keywords

  • Coding DNA sequence
  • lineage
  • lymphadenitis
  • nonsynonymous
  • octal code

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Genetics

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  • Cite this

    Sharma, K., Verma, R., Advani, J., Chatterjee, O., Solanki, H. S., Sharma, A., Varma, S., Modi, M., Ray, P., Mukherjee, K. K., Sharma, M., Dhillion, M. S., Suar, M., Chatterjee, A., Pandey, A., Prasad, T. S. K., & Gowda, H. (2017). Whole Genome Sequencing of Mycobacterium tuberculosis Isolates from Extrapulmonary Sites. OMICS A Journal of Integrative Biology, 21(7), 413-425. https://doi.org/10.1089/omi.2017.0070