Integrated Multi-Omic Analysis of Mycobacterium tuberculosis H37Ra Redefines Virulence Attributes
H37Ra is a virulence attenuated strain of Mycobacterium tuberculosis widely employed as a model to investigate virulence mechanisms. Comparative high-throughput studies have earlier correlated its avirulence to the presence of specific mutations or absence of certain proteins. However, a recent sequ...
Main Authors: | , , , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Frontiers Media S.A.
2018-06-01
|
Series: | Frontiers in Microbiology |
Subjects: | |
Online Access: | https://www.frontiersin.org/article/10.3389/fmicb.2018.01314/full |
id |
doaj-84d10973e0f549abb246d516ea3f91e9 |
---|---|
record_format |
Article |
spelling |
doaj-84d10973e0f549abb246d516ea3f91e92020-11-24T23:18:02ZengFrontiers Media S.A.Frontiers in Microbiology1664-302X2018-06-01910.3389/fmicb.2018.01314363237Integrated Multi-Omic Analysis of Mycobacterium tuberculosis H37Ra Redefines Virulence AttributesSneha M. Pinto0Renu Verma1Jayshree Advani2Jayshree Advani3Oishi Chatterjee4Oishi Chatterjee5Oishi Chatterjee6Arun H. Patil7Arun H. Patil8Arun H. Patil9Saketh Kapoor10Yashwanth Subbannayya11Remya Raja12Sheetal Gandotra13T. S. Keshava Prasad14T. S. Keshava Prasad15Center for Systems Biology and Molecular Medicine, Yenepoya (Deemed to be University), Mangalore, IndiaInstitute of Bioinformatics, International Technology Park, Bangalore, IndiaInstitute of Bioinformatics, International Technology Park, Bangalore, IndiaManipal Academy of Higher Education, Manipal, IndiaCenter for Systems Biology and Molecular Medicine, Yenepoya (Deemed to be University), Mangalore, IndiaInstitute of Bioinformatics, International Technology Park, Bangalore, IndiaSchool of Biotechnology, Amrita Vishwa Vidyapeetham, Kollam, IndiaCenter for Systems Biology and Molecular Medicine, Yenepoya (Deemed to be University), Mangalore, IndiaInstitute of Bioinformatics, International Technology Park, Bangalore, IndiaSchool of Biotechnology, KIIT University, Bhubaneswar, IndiaCenter for Systems Biology and Molecular Medicine, Yenepoya (Deemed to be University), Mangalore, IndiaCenter for Systems Biology and Molecular Medicine, Yenepoya (Deemed to be University), Mangalore, IndiaInstitute of Bioinformatics, International Technology Park, Bangalore, IndiaCSIR-Institute of Genomics and Integrative Biology, New Delhi, IndiaCenter for Systems Biology and Molecular Medicine, Yenepoya (Deemed to be University), Mangalore, IndiaInstitute of Bioinformatics, International Technology Park, Bangalore, IndiaH37Ra is a virulence attenuated strain of Mycobacterium tuberculosis widely employed as a model to investigate virulence mechanisms. Comparative high-throughput studies have earlier correlated its avirulence to the presence of specific mutations or absence of certain proteins. However, a recent sequencing study of H37Ra, has disproved several genomic differences earlier reported to be associated with virulence. This warrants further investigations on the H37Ra proteome as well. In this study, we carried out an integrated analysis of the genome, transcriptome, and proteome of H37Ra. In addition to confirming single nucleotide variations (SNVs) and insertion-deletions that were reported earlier, our study provides novel insights into the mutation spectrum in the promoter regions of 7 genes. We also provide transcriptional and proteomic evidence for 3,900 genes representing ~80% of the total predicted gene count including 408 proteins that have not been identified previously. We identified 9 genes whose coding potential was hitherto reported to be absent in H37Ra. These include 2 putative virulence factors belonging to ESAT-6 like family of proteins. Furthermore, proteogenomic analysis enabled us to identify 63 novel proteins coding genes and correct 25 existing gene models in H37Ra genome. A majority of these were found to be conserved in the virulent strain H37Rv as well as in other mycobacterial species suggesting that the differences in the virulent and avirulent strains of M. tuberculosis are not entirely dependent on the expression of certain proteins or their absence but may possibly be ascertained to functional changes.https://www.frontiersin.org/article/10.3389/fmicb.2018.01314/fullnext-generation sequencingorbitrapgenome annotationvirulence attenuationmultiomics |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Sneha M. Pinto Renu Verma Jayshree Advani Jayshree Advani Oishi Chatterjee Oishi Chatterjee Oishi Chatterjee Arun H. Patil Arun H. Patil Arun H. Patil Saketh Kapoor Yashwanth Subbannayya Remya Raja Sheetal Gandotra T. S. Keshava Prasad T. S. Keshava Prasad |
spellingShingle |
Sneha M. Pinto Renu Verma Jayshree Advani Jayshree Advani Oishi Chatterjee Oishi Chatterjee Oishi Chatterjee Arun H. Patil Arun H. Patil Arun H. Patil Saketh Kapoor Yashwanth Subbannayya Remya Raja Sheetal Gandotra T. S. Keshava Prasad T. S. Keshava Prasad Integrated Multi-Omic Analysis of Mycobacterium tuberculosis H37Ra Redefines Virulence Attributes Frontiers in Microbiology next-generation sequencing orbitrap genome annotation virulence attenuation multiomics |
author_facet |
Sneha M. Pinto Renu Verma Jayshree Advani Jayshree Advani Oishi Chatterjee Oishi Chatterjee Oishi Chatterjee Arun H. Patil Arun H. Patil Arun H. Patil Saketh Kapoor Yashwanth Subbannayya Remya Raja Sheetal Gandotra T. S. Keshava Prasad T. S. Keshava Prasad |
author_sort |
Sneha M. Pinto |
title |
Integrated Multi-Omic Analysis of Mycobacterium tuberculosis H37Ra Redefines Virulence Attributes |
title_short |
Integrated Multi-Omic Analysis of Mycobacterium tuberculosis H37Ra Redefines Virulence Attributes |
title_full |
Integrated Multi-Omic Analysis of Mycobacterium tuberculosis H37Ra Redefines Virulence Attributes |
title_fullStr |
Integrated Multi-Omic Analysis of Mycobacterium tuberculosis H37Ra Redefines Virulence Attributes |
title_full_unstemmed |
Integrated Multi-Omic Analysis of Mycobacterium tuberculosis H37Ra Redefines Virulence Attributes |
title_sort |
integrated multi-omic analysis of mycobacterium tuberculosis h37ra redefines virulence attributes |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Microbiology |
issn |
1664-302X |
publishDate |
2018-06-01 |
description |
H37Ra is a virulence attenuated strain of Mycobacterium tuberculosis widely employed as a model to investigate virulence mechanisms. Comparative high-throughput studies have earlier correlated its avirulence to the presence of specific mutations or absence of certain proteins. However, a recent sequencing study of H37Ra, has disproved several genomic differences earlier reported to be associated with virulence. This warrants further investigations on the H37Ra proteome as well. In this study, we carried out an integrated analysis of the genome, transcriptome, and proteome of H37Ra. In addition to confirming single nucleotide variations (SNVs) and insertion-deletions that were reported earlier, our study provides novel insights into the mutation spectrum in the promoter regions of 7 genes. We also provide transcriptional and proteomic evidence for 3,900 genes representing ~80% of the total predicted gene count including 408 proteins that have not been identified previously. We identified 9 genes whose coding potential was hitherto reported to be absent in H37Ra. These include 2 putative virulence factors belonging to ESAT-6 like family of proteins. Furthermore, proteogenomic analysis enabled us to identify 63 novel proteins coding genes and correct 25 existing gene models in H37Ra genome. A majority of these were found to be conserved in the virulent strain H37Rv as well as in other mycobacterial species suggesting that the differences in the virulent and avirulent strains of M. tuberculosis are not entirely dependent on the expression of certain proteins or their absence but may possibly be ascertained to functional changes. |
topic |
next-generation sequencing orbitrap genome annotation virulence attenuation multiomics |
url |
https://www.frontiersin.org/article/10.3389/fmicb.2018.01314/full |
work_keys_str_mv |
AT snehampinto integratedmultiomicanalysisofmycobacteriumtuberculosish37raredefinesvirulenceattributes AT renuverma integratedmultiomicanalysisofmycobacteriumtuberculosish37raredefinesvirulenceattributes AT jayshreeadvani integratedmultiomicanalysisofmycobacteriumtuberculosish37raredefinesvirulenceattributes AT jayshreeadvani integratedmultiomicanalysisofmycobacteriumtuberculosish37raredefinesvirulenceattributes AT oishichatterjee integratedmultiomicanalysisofmycobacteriumtuberculosish37raredefinesvirulenceattributes AT oishichatterjee integratedmultiomicanalysisofmycobacteriumtuberculosish37raredefinesvirulenceattributes AT oishichatterjee integratedmultiomicanalysisofmycobacteriumtuberculosish37raredefinesvirulenceattributes AT arunhpatil integratedmultiomicanalysisofmycobacteriumtuberculosish37raredefinesvirulenceattributes AT arunhpatil integratedmultiomicanalysisofmycobacteriumtuberculosish37raredefinesvirulenceattributes AT arunhpatil integratedmultiomicanalysisofmycobacteriumtuberculosish37raredefinesvirulenceattributes AT sakethkapoor integratedmultiomicanalysisofmycobacteriumtuberculosish37raredefinesvirulenceattributes AT yashwanthsubbannayya integratedmultiomicanalysisofmycobacteriumtuberculosish37raredefinesvirulenceattributes AT remyaraja integratedmultiomicanalysisofmycobacteriumtuberculosish37raredefinesvirulenceattributes AT sheetalgandotra integratedmultiomicanalysisofmycobacteriumtuberculosish37raredefinesvirulenceattributes AT tskeshavaprasad integratedmultiomicanalysisofmycobacteriumtuberculosish37raredefinesvirulenceattributes AT tskeshavaprasad integratedmultiomicanalysisofmycobacteriumtuberculosish37raredefinesvirulenceattributes |
_version_ |
1725582136210096128 |