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Transcriptome Analysis of Enterococcus faecalis during Mammalian Infection Shows Cells Undergo Adaptation and Exist in a Stringent Response State
As both a commensal and a major cause of healthcare-associated infections in humans, Enterococcus faecalis is a remarkably adaptable organism. We investigated how E. faecalis adapts in a mammalian host as a pathogen by characterizing changes in the transcriptome during infection in a rabbit model of...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4278851/ https://www.ncbi.nlm.nih.gov/pubmed/25545155 http://dx.doi.org/10.1371/journal.pone.0115839 |
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author | Frank, Kristi L. Colomer-Winter, Cristina Grindle, Suzanne M. Lemos, José A. Schlievert, Patrick M. Dunny, Gary M. |
author_facet | Frank, Kristi L. Colomer-Winter, Cristina Grindle, Suzanne M. Lemos, José A. Schlievert, Patrick M. Dunny, Gary M. |
author_sort | Frank, Kristi L. |
collection | PubMed |
description | As both a commensal and a major cause of healthcare-associated infections in humans, Enterococcus faecalis is a remarkably adaptable organism. We investigated how E. faecalis adapts in a mammalian host as a pathogen by characterizing changes in the transcriptome during infection in a rabbit model of subdermal abscess formation using transcriptional microarrays. The microarray experiments detected 222 and 291 differentially regulated genes in E. faecalis OG1RF at two and eight hours after subdermal chamber inoculation, respectively. The profile of significantly regulated genes at two hours post-inoculation included genes involved in stress response, metabolism, nutrient acquisition, and cell surface components, suggesting genome-wide adaptation to growth in an altered environment. At eight hours post-inoculation, 88% of the differentially expressed genes were down-regulated and matched a transcriptional profile consistent with a (p)ppGpp-mediated stringent response. Subsequent subdermal abscess infections with E. faecalis mutants lacking the (p)ppGpp synthetase/hydrolase RSH, the small synthetase RelQ, or both enzymes, suggest that intracellular (p)ppGpp levels, but not stringent response activation, influence persistence in the model. The ability of cells to synthesize (p)ppGpp was also found to be important for growth in human serum and whole blood. The data presented in this report provide the first genome-wide insights on E. faecalis in vivo gene expression and regulation measured by transcriptional profiling during infection in a mammalian host and show that (p)ppGpp levels affect viability of E. faecalis in multiple conditions relevant to mammalian infection. The subdermal abscess model can serve as a novel experimental system for studying the E. faecalis stringent response in the context of the mammalian immune system. |
format | Online Article Text |
id | pubmed-4278851 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-42788512015-01-05 Transcriptome Analysis of Enterococcus faecalis during Mammalian Infection Shows Cells Undergo Adaptation and Exist in a Stringent Response State Frank, Kristi L. Colomer-Winter, Cristina Grindle, Suzanne M. Lemos, José A. Schlievert, Patrick M. Dunny, Gary M. PLoS One Research Article As both a commensal and a major cause of healthcare-associated infections in humans, Enterococcus faecalis is a remarkably adaptable organism. We investigated how E. faecalis adapts in a mammalian host as a pathogen by characterizing changes in the transcriptome during infection in a rabbit model of subdermal abscess formation using transcriptional microarrays. The microarray experiments detected 222 and 291 differentially regulated genes in E. faecalis OG1RF at two and eight hours after subdermal chamber inoculation, respectively. The profile of significantly regulated genes at two hours post-inoculation included genes involved in stress response, metabolism, nutrient acquisition, and cell surface components, suggesting genome-wide adaptation to growth in an altered environment. At eight hours post-inoculation, 88% of the differentially expressed genes were down-regulated and matched a transcriptional profile consistent with a (p)ppGpp-mediated stringent response. Subsequent subdermal abscess infections with E. faecalis mutants lacking the (p)ppGpp synthetase/hydrolase RSH, the small synthetase RelQ, or both enzymes, suggest that intracellular (p)ppGpp levels, but not stringent response activation, influence persistence in the model. The ability of cells to synthesize (p)ppGpp was also found to be important for growth in human serum and whole blood. The data presented in this report provide the first genome-wide insights on E. faecalis in vivo gene expression and regulation measured by transcriptional profiling during infection in a mammalian host and show that (p)ppGpp levels affect viability of E. faecalis in multiple conditions relevant to mammalian infection. The subdermal abscess model can serve as a novel experimental system for studying the E. faecalis stringent response in the context of the mammalian immune system. Public Library of Science 2014-12-29 /pmc/articles/PMC4278851/ /pubmed/25545155 http://dx.doi.org/10.1371/journal.pone.0115839 Text en © 2014 Frank 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, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Frank, Kristi L. Colomer-Winter, Cristina Grindle, Suzanne M. Lemos, José A. Schlievert, Patrick M. Dunny, Gary M. Transcriptome Analysis of Enterococcus faecalis during Mammalian Infection Shows Cells Undergo Adaptation and Exist in a Stringent Response State |
title | Transcriptome Analysis of Enterococcus faecalis during Mammalian Infection Shows Cells Undergo Adaptation and Exist in a Stringent Response State |
title_full | Transcriptome Analysis of Enterococcus faecalis during Mammalian Infection Shows Cells Undergo Adaptation and Exist in a Stringent Response State |
title_fullStr | Transcriptome Analysis of Enterococcus faecalis during Mammalian Infection Shows Cells Undergo Adaptation and Exist in a Stringent Response State |
title_full_unstemmed | Transcriptome Analysis of Enterococcus faecalis during Mammalian Infection Shows Cells Undergo Adaptation and Exist in a Stringent Response State |
title_short | Transcriptome Analysis of Enterococcus faecalis during Mammalian Infection Shows Cells Undergo Adaptation and Exist in a Stringent Response State |
title_sort | transcriptome analysis of enterococcus faecalis during mammalian infection shows cells undergo adaptation and exist in a stringent response state |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4278851/ https://www.ncbi.nlm.nih.gov/pubmed/25545155 http://dx.doi.org/10.1371/journal.pone.0115839 |
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