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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...

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Autores principales: Pinto, Sneha M., Verma, Renu, Advani, Jayshree, Chatterjee, Oishi, Patil, Arun H., Kapoor, Saketh, Subbannayya, Yashwanth, Raja, Remya, Gandotra, Sheetal, Prasad, T. S. Keshava
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6018540/
https://www.ncbi.nlm.nih.gov/pubmed/29971057
http://dx.doi.org/10.3389/fmicb.2018.01314
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author Pinto, Sneha M.
Verma, Renu
Advani, Jayshree
Chatterjee, Oishi
Patil, Arun H.
Kapoor, Saketh
Subbannayya, Yashwanth
Raja, Remya
Gandotra, Sheetal
Prasad, T. S. Keshava
author_facet Pinto, Sneha M.
Verma, Renu
Advani, Jayshree
Chatterjee, Oishi
Patil, Arun H.
Kapoor, Saketh
Subbannayya, Yashwanth
Raja, Remya
Gandotra, Sheetal
Prasad, T. S. Keshava
author_sort Pinto, Sneha M.
collection PubMed
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.
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spelling pubmed-60185402018-07-03 Integrated Multi-Omic Analysis of Mycobacterium tuberculosis H37Ra Redefines Virulence Attributes Pinto, Sneha M. Verma, Renu Advani, Jayshree Chatterjee, Oishi Patil, Arun H. Kapoor, Saketh Subbannayya, Yashwanth Raja, Remya Gandotra, Sheetal Prasad, T. S. Keshava Front Microbiol Microbiology 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. Frontiers Media S.A. 2018-06-19 /pmc/articles/PMC6018540/ /pubmed/29971057 http://dx.doi.org/10.3389/fmicb.2018.01314 Text en Copyright © 2018 Pinto, Verma, Advani, Chatterjee, Patil, Kapoor, Subbannayya, Raja, Gandotra and Prasad. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Microbiology
Pinto, Sneha M.
Verma, Renu
Advani, Jayshree
Chatterjee, Oishi
Patil, Arun H.
Kapoor, Saketh
Subbannayya, Yashwanth
Raja, Remya
Gandotra, Sheetal
Prasad, T. S. Keshava
Integrated Multi-Omic Analysis of Mycobacterium tuberculosis H37Ra Redefines Virulence Attributes
title 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_short Integrated Multi-Omic Analysis of Mycobacterium tuberculosis H37Ra Redefines Virulence Attributes
title_sort integrated multi-omic analysis of mycobacterium tuberculosis h37ra redefines virulence attributes
topic Microbiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6018540/
https://www.ncbi.nlm.nih.gov/pubmed/29971057
http://dx.doi.org/10.3389/fmicb.2018.01314
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