Contrasting transcriptional responses of a virulent and an attenuated strain of Mycobacterium tuberculosis infecting macrophages.
<h4>Background</h4>H37Rv and H37Ra are well-described laboratory strains of Mycobacterium tuberculosis derived from the same parental strain, H37, that show dramatically different pathogenic phenotypes.<h4>Methodology/principal findings</h4>In this study, the transcriptomes o...
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Public Library of Science (PLoS)
2010-06-01
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| author | Alice H Li Simon J Waddell Jason Hinds Chad A Malloff Manjeet Bains Robert E Hancock Wan L Lam Philip D Butcher Richard W Stokes |
| author_facet | Alice H Li Simon J Waddell Jason Hinds Chad A Malloff Manjeet Bains Robert E Hancock Wan L Lam Philip D Butcher Richard W Stokes |
| author_sort | Alice H Li |
| collection | DOAJ |
| description | <h4>Background</h4>H37Rv and H37Ra are well-described laboratory strains of Mycobacterium tuberculosis derived from the same parental strain, H37, that show dramatically different pathogenic phenotypes.<h4>Methodology/principal findings</h4>In this study, the transcriptomes of the two strains during axenic growth in broth and during intracellular growth within murine bone-marrow macrophages were compared by whole genome expression profiling. We identified and compared adaptations of either strain upon encountering an intracellular environment, and also contrasted the transcriptomes of the two strains while inside macrophages. In the former comparison, both strains induced genes that would facilitate intracellular survival including those involved in mycobactin synthesis and fatty acid metabolism. However, this response was stronger and more extensive for H37Rv than for H37Ra. This was manifested as the differential expression of a greater number of genes and an increased magnitude of expression for these genes in H37Rv. In comparing intracellular transcriptional signatures, fifty genes were found to be differentially expressed between the strains. Of these fifty, twelve were under control of the PhoPR regulon. Further differences between strains included genes whose products were members of the ESAT-6 family of proteins, or were associated with their secretion.<h4>Conclusions/significance</h4>Along with the recent identification of single nucleotide polymorphisms in H37Ra when compared to H37Rv, our demonstration of differential expression of PhoP-regulated and ESX-1 region-related genes during macrophage infection further highlights the significance of these genes in the attenuation of H37Ra. |
| format | Article |
| id | doaj-art-780a64bf82654027a3fca32b503b54a2 |
| institution | OA Journals |
| issn | 1932-6203 |
| language | English |
| publishDate | 2010-06-01 |
| publisher | Public Library of Science (PLoS) |
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| series | PLoS ONE |
| spelling | doaj-art-780a64bf82654027a3fca32b503b54a22025-08-20T02:01:58ZengPublic Library of Science (PLoS)PLoS ONE1932-62032010-06-0156e1106610.1371/journal.pone.0011066Contrasting transcriptional responses of a virulent and an attenuated strain of Mycobacterium tuberculosis infecting macrophages.Alice H LiSimon J WaddellJason HindsChad A MalloffManjeet BainsRobert E HancockWan L LamPhilip D ButcherRichard W Stokes<h4>Background</h4>H37Rv and H37Ra are well-described laboratory strains of Mycobacterium tuberculosis derived from the same parental strain, H37, that show dramatically different pathogenic phenotypes.<h4>Methodology/principal findings</h4>In this study, the transcriptomes of the two strains during axenic growth in broth and during intracellular growth within murine bone-marrow macrophages were compared by whole genome expression profiling. We identified and compared adaptations of either strain upon encountering an intracellular environment, and also contrasted the transcriptomes of the two strains while inside macrophages. In the former comparison, both strains induced genes that would facilitate intracellular survival including those involved in mycobactin synthesis and fatty acid metabolism. However, this response was stronger and more extensive for H37Rv than for H37Ra. This was manifested as the differential expression of a greater number of genes and an increased magnitude of expression for these genes in H37Rv. In comparing intracellular transcriptional signatures, fifty genes were found to be differentially expressed between the strains. Of these fifty, twelve were under control of the PhoPR regulon. Further differences between strains included genes whose products were members of the ESAT-6 family of proteins, or were associated with their secretion.<h4>Conclusions/significance</h4>Along with the recent identification of single nucleotide polymorphisms in H37Ra when compared to H37Rv, our demonstration of differential expression of PhoP-regulated and ESX-1 region-related genes during macrophage infection further highlights the significance of these genes in the attenuation of H37Ra.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0011066&type=printable |
| spellingShingle | Alice H Li Simon J Waddell Jason Hinds Chad A Malloff Manjeet Bains Robert E Hancock Wan L Lam Philip D Butcher Richard W Stokes Contrasting transcriptional responses of a virulent and an attenuated strain of Mycobacterium tuberculosis infecting macrophages. PLoS ONE |
| title | Contrasting transcriptional responses of a virulent and an attenuated strain of Mycobacterium tuberculosis infecting macrophages. |
| title_full | Contrasting transcriptional responses of a virulent and an attenuated strain of Mycobacterium tuberculosis infecting macrophages. |
| title_fullStr | Contrasting transcriptional responses of a virulent and an attenuated strain of Mycobacterium tuberculosis infecting macrophages. |
| title_full_unstemmed | Contrasting transcriptional responses of a virulent and an attenuated strain of Mycobacterium tuberculosis infecting macrophages. |
| title_short | Contrasting transcriptional responses of a virulent and an attenuated strain of Mycobacterium tuberculosis infecting macrophages. |
| title_sort | contrasting transcriptional responses of a virulent and an attenuated strain of mycobacterium tuberculosis infecting macrophages |
| url | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0011066&type=printable |
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