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Chromosomal rearrangements and protein globularity changes in Mycobacterium tuberculosis isolates from cerebrospinal fluid
BACKGROUND: Meningitis is a major cause of mortality in tuberculosis (TB). It is not clear what factors promote central nervous system invasion and pathology but it has been reported that certain strains of Mycobacterium tuberculosis (Mtb) might have genetic traits associated with neurotropism. METH...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
PeerJ Inc.
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5036109/ https://www.ncbi.nlm.nih.gov/pubmed/27688977 http://dx.doi.org/10.7717/peerj.2484 |
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author | Saw, Seow Hoon Tan, Joon Liang Chan, Xin Yue Chan, Kok Gan Ngeow, Yun Fong |
author_facet | Saw, Seow Hoon Tan, Joon Liang Chan, Xin Yue Chan, Kok Gan Ngeow, Yun Fong |
author_sort | Saw, Seow Hoon |
collection | PubMed |
description | BACKGROUND: Meningitis is a major cause of mortality in tuberculosis (TB). It is not clear what factors promote central nervous system invasion and pathology but it has been reported that certain strains of Mycobacterium tuberculosis (Mtb) might have genetic traits associated with neurotropism. METHODS: In this study, we generated whole genome sequences of eight clinical strains of Mtb that were isolated from the cerebrospinal fluid (CSF) of patients presenting with tuberculous meningitis (TBM) in Malaysia, and compared them to the genomes of H37Rv and other respiratory Mtb genomes either downloaded from public databases or extracted from local sputum isolates. We aimed to find genomic features that might be distinctly different between CSF-derived and respiratory Mtb. RESULTS: Genome-wide comparisons revealed rearrangements (translocations, inversions, insertions and deletions) and non-synonymous SNPs in our CSF-derived strains that were not observed in the respiratory Mtb genomes used for comparison. These rearranged segments were rich in genes for PE (proline-glutamate)/PPE (proline-proline-glutamate), transcriptional and membrane proteins. Similarly, most of the ns SNPs common in CSF strains were noted in genes encoding PE/PPE proteins. Protein globularity differences were observed among mycobacteria from CSF and respiratory sources and in proteins previously reported to be associated with TB meningitis. Transcription factors and other transcription regulators featured prominently in these proteins. Homologs of proteins associated with Streptococcus pneumoniae meningitis and Neisseria meningitidis virulence were identified in neuropathogenic as well as respiratory mycobacterial spp. examined in this study. DISCUSSION: The occurrence of in silico genetic differences in CSF-derived but not respiratory Mtb suggests their possible involvement in the pathogenesis of TBM. However, overall findings in this comparative analysis support the postulation that TB meningeal infection is more likely to be related to the expression of multiple virulence factors on interaction with host defences than to CNS tropism associated with specific genetic traits. |
format | Online Article Text |
id | pubmed-5036109 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | PeerJ Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-50361092016-09-29 Chromosomal rearrangements and protein globularity changes in Mycobacterium tuberculosis isolates from cerebrospinal fluid Saw, Seow Hoon Tan, Joon Liang Chan, Xin Yue Chan, Kok Gan Ngeow, Yun Fong PeerJ Bioinformatics BACKGROUND: Meningitis is a major cause of mortality in tuberculosis (TB). It is not clear what factors promote central nervous system invasion and pathology but it has been reported that certain strains of Mycobacterium tuberculosis (Mtb) might have genetic traits associated with neurotropism. METHODS: In this study, we generated whole genome sequences of eight clinical strains of Mtb that were isolated from the cerebrospinal fluid (CSF) of patients presenting with tuberculous meningitis (TBM) in Malaysia, and compared them to the genomes of H37Rv and other respiratory Mtb genomes either downloaded from public databases or extracted from local sputum isolates. We aimed to find genomic features that might be distinctly different between CSF-derived and respiratory Mtb. RESULTS: Genome-wide comparisons revealed rearrangements (translocations, inversions, insertions and deletions) and non-synonymous SNPs in our CSF-derived strains that were not observed in the respiratory Mtb genomes used for comparison. These rearranged segments were rich in genes for PE (proline-glutamate)/PPE (proline-proline-glutamate), transcriptional and membrane proteins. Similarly, most of the ns SNPs common in CSF strains were noted in genes encoding PE/PPE proteins. Protein globularity differences were observed among mycobacteria from CSF and respiratory sources and in proteins previously reported to be associated with TB meningitis. Transcription factors and other transcription regulators featured prominently in these proteins. Homologs of proteins associated with Streptococcus pneumoniae meningitis and Neisseria meningitidis virulence were identified in neuropathogenic as well as respiratory mycobacterial spp. examined in this study. DISCUSSION: The occurrence of in silico genetic differences in CSF-derived but not respiratory Mtb suggests their possible involvement in the pathogenesis of TBM. However, overall findings in this comparative analysis support the postulation that TB meningeal infection is more likely to be related to the expression of multiple virulence factors on interaction with host defences than to CNS tropism associated with specific genetic traits. PeerJ Inc. 2016-09-21 /pmc/articles/PMC5036109/ /pubmed/27688977 http://dx.doi.org/10.7717/peerj.2484 Text en © 2016 Saw et al. http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, reproduction and adaptation in any medium and for any purpose provided that it is properly attributed. For attribution, the original author(s), title, publication source (PeerJ) and either DOI or URL of the article must be cited. |
spellingShingle | Bioinformatics Saw, Seow Hoon Tan, Joon Liang Chan, Xin Yue Chan, Kok Gan Ngeow, Yun Fong Chromosomal rearrangements and protein globularity changes in Mycobacterium tuberculosis isolates from cerebrospinal fluid |
title | Chromosomal rearrangements and protein globularity changes in Mycobacterium tuberculosis isolates from cerebrospinal fluid |
title_full | Chromosomal rearrangements and protein globularity changes in Mycobacterium tuberculosis isolates from cerebrospinal fluid |
title_fullStr | Chromosomal rearrangements and protein globularity changes in Mycobacterium tuberculosis isolates from cerebrospinal fluid |
title_full_unstemmed | Chromosomal rearrangements and protein globularity changes in Mycobacterium tuberculosis isolates from cerebrospinal fluid |
title_short | Chromosomal rearrangements and protein globularity changes in Mycobacterium tuberculosis isolates from cerebrospinal fluid |
title_sort | chromosomal rearrangements and protein globularity changes in mycobacterium tuberculosis isolates from cerebrospinal fluid |
topic | Bioinformatics |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5036109/ https://www.ncbi.nlm.nih.gov/pubmed/27688977 http://dx.doi.org/10.7717/peerj.2484 |
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