Non-replicating Mycobacterium tuberculosis elicits a reduced infectivity profile with corresponding modifications to the cell wall and extracellular matrix.
A key feature of Mycobacterium tuberculosis is its ability to become dormant in the host. Little is known of the mechanisms by which these bacilli are able to persist in this state. Therefore, the focus of this study was to emulate environmental conditions encountered by M. tuberculosis in the granu...
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| Language: | English |
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Public Library of Science (PLoS)
2014-01-01
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| Series: | PLoS ONE |
| Online Access: | https://doi.org/10.1371/journal.pone.0087329 |
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| author | Joanna Bacon Luke J Alderwick Jon A Allnutt Evelina Gabasova Robert Watson Kim A Hatch Simon O Clark Rose E Jeeves Alice Marriott Emma Rayner Howard Tolley Geoff Pearson Graham Hall Gurdyal S Besra Lorenz Wernisch Ann Williams Philip D Marsh |
| author_facet | Joanna Bacon Luke J Alderwick Jon A Allnutt Evelina Gabasova Robert Watson Kim A Hatch Simon O Clark Rose E Jeeves Alice Marriott Emma Rayner Howard Tolley Geoff Pearson Graham Hall Gurdyal S Besra Lorenz Wernisch Ann Williams Philip D Marsh |
| author_sort | Joanna Bacon |
| collection | DOAJ |
| description | A key feature of Mycobacterium tuberculosis is its ability to become dormant in the host. Little is known of the mechanisms by which these bacilli are able to persist in this state. Therefore, the focus of this study was to emulate environmental conditions encountered by M. tuberculosis in the granuloma, and determine the effect of such conditions on the physiology and infectivity of the organism. Non-replicating persistent (NRP) M. tuberculosis was established by the gradual depletion of nutrients in an oxygen-replete and controlled environment. In contrast to rapidly dividing bacilli, NRP bacteria exhibited a distinct phenotype by accumulating an extracellular matrix rich in free mycolate and lipoglycans, with increased arabinosylation. Microarray studies demonstrated a substantial down-regulation of genes involved in energy metabolism in NRP bacteria. Despite this reduction in metabolic activity, cells were still able to infect guinea pigs, but with a delay in the development of disease when compared to exponential phase bacilli. Using these approaches to investigate the interplay between the changing environment of the host and altered physiology of NRP bacteria, this study sheds new light on the conditions that are pertinent to M. tuberculosis dormancy and how this organism could be establishing latent disease. |
| format | Article |
| id | doaj-art-c11cea27e6004c5da7415a8a6a12a1b4 |
| institution | OA Journals |
| issn | 1932-6203 |
| language | English |
| publishDate | 2014-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj-art-c11cea27e6004c5da7415a8a6a12a1b42025-08-20T02:22:37ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-0192e8732910.1371/journal.pone.0087329Non-replicating Mycobacterium tuberculosis elicits a reduced infectivity profile with corresponding modifications to the cell wall and extracellular matrix.Joanna BaconLuke J AlderwickJon A AllnuttEvelina GabasovaRobert WatsonKim A HatchSimon O ClarkRose E JeevesAlice MarriottEmma RaynerHoward TolleyGeoff PearsonGraham HallGurdyal S BesraLorenz WernischAnn WilliamsPhilip D MarshA key feature of Mycobacterium tuberculosis is its ability to become dormant in the host. Little is known of the mechanisms by which these bacilli are able to persist in this state. Therefore, the focus of this study was to emulate environmental conditions encountered by M. tuberculosis in the granuloma, and determine the effect of such conditions on the physiology and infectivity of the organism. Non-replicating persistent (NRP) M. tuberculosis was established by the gradual depletion of nutrients in an oxygen-replete and controlled environment. In contrast to rapidly dividing bacilli, NRP bacteria exhibited a distinct phenotype by accumulating an extracellular matrix rich in free mycolate and lipoglycans, with increased arabinosylation. Microarray studies demonstrated a substantial down-regulation of genes involved in energy metabolism in NRP bacteria. Despite this reduction in metabolic activity, cells were still able to infect guinea pigs, but with a delay in the development of disease when compared to exponential phase bacilli. Using these approaches to investigate the interplay between the changing environment of the host and altered physiology of NRP bacteria, this study sheds new light on the conditions that are pertinent to M. tuberculosis dormancy and how this organism could be establishing latent disease.https://doi.org/10.1371/journal.pone.0087329 |
| spellingShingle | Joanna Bacon Luke J Alderwick Jon A Allnutt Evelina Gabasova Robert Watson Kim A Hatch Simon O Clark Rose E Jeeves Alice Marriott Emma Rayner Howard Tolley Geoff Pearson Graham Hall Gurdyal S Besra Lorenz Wernisch Ann Williams Philip D Marsh Non-replicating Mycobacterium tuberculosis elicits a reduced infectivity profile with corresponding modifications to the cell wall and extracellular matrix. PLoS ONE |
| title | Non-replicating Mycobacterium tuberculosis elicits a reduced infectivity profile with corresponding modifications to the cell wall and extracellular matrix. |
| title_full | Non-replicating Mycobacterium tuberculosis elicits a reduced infectivity profile with corresponding modifications to the cell wall and extracellular matrix. |
| title_fullStr | Non-replicating Mycobacterium tuberculosis elicits a reduced infectivity profile with corresponding modifications to the cell wall and extracellular matrix. |
| title_full_unstemmed | Non-replicating Mycobacterium tuberculosis elicits a reduced infectivity profile with corresponding modifications to the cell wall and extracellular matrix. |
| title_short | Non-replicating Mycobacterium tuberculosis elicits a reduced infectivity profile with corresponding modifications to the cell wall and extracellular matrix. |
| title_sort | non replicating mycobacterium tuberculosis elicits a reduced infectivity profile with corresponding modifications to the cell wall and extracellular matrix |
| url | https://doi.org/10.1371/journal.pone.0087329 |
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