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Influence of the Alternative Sigma Factor RpoN on Global Gene Expression and Carbon Catabolism in Enterococcus faecalis V583

The alternative sigma factor σ(54) has been shown to regulate the expression of a wide array of virulence-associated genes, as well as central metabolism, in bacterial pathogens. In Gram-positive organisms, the σ(54) is commonly associated with carbon metabolism. In this study, we show that the Ente...

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Autores principales: Keffeler, Erica C., Iyer, Vijayalakshmi S., Parthasarathy, Srivatsan, Ramsey, Matthew M., Gorman, Matthew J., Barke, Theresa L., Varahan, Sriram, Olson, Sally, Gilmore, Michael S., Abdullahi, Zakria H., Hancock, Emmaleigh N., Hancock, Lynn E.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society for Microbiology 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8262876/
https://www.ncbi.nlm.nih.gov/pubmed/34006651
http://dx.doi.org/10.1128/mBio.00380-21
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author Keffeler, Erica C.
Iyer, Vijayalakshmi S.
Parthasarathy, Srivatsan
Ramsey, Matthew M.
Gorman, Matthew J.
Barke, Theresa L.
Varahan, Sriram
Olson, Sally
Gilmore, Michael S.
Abdullahi, Zakria H.
Hancock, Emmaleigh N.
Hancock, Lynn E.
author_facet Keffeler, Erica C.
Iyer, Vijayalakshmi S.
Parthasarathy, Srivatsan
Ramsey, Matthew M.
Gorman, Matthew J.
Barke, Theresa L.
Varahan, Sriram
Olson, Sally
Gilmore, Michael S.
Abdullahi, Zakria H.
Hancock, Emmaleigh N.
Hancock, Lynn E.
author_sort Keffeler, Erica C.
collection PubMed
description The alternative sigma factor σ(54) has been shown to regulate the expression of a wide array of virulence-associated genes, as well as central metabolism, in bacterial pathogens. In Gram-positive organisms, the σ(54) is commonly associated with carbon metabolism. In this study, we show that the Enterococcus faecalis alternative sigma factor σ(54) (RpoN) and its cognate enhancer binding protein MptR are essential for mannose utilization and are primary contributors to glucose uptake through the Mpt phosphotransferase system. To gain further insight into how RpoN contributes to global transcriptional changes, we performed microarray transcriptional analysis of strain V583 and an isogenic rpoN mutant grown in a chemically defined medium with glucose as the sole carbon source. Transcripts of 340 genes were differentially affected in the rpoN mutant; the predicted functions of these genes mainly related to nutrient acquisition. These differentially expressed genes included those with predicted catabolite-responsive element (cre) sites, consistent with loss of repression by the major carbon catabolite repressor CcpA. To determine if the inability to efficiently metabolize glucose/mannose affected infection outcome, we utilized two distinct infection models. We found that the rpoN mutant is significantly attenuated in both rabbit endocarditis and murine catheter-associated urinary tract infection (CAUTI). Here, we examined a ccpA mutant in the CAUTI model and showed that the absence of carbon catabolite control also significantly attenuates bacterial tissue burden in this model. Our data highlight the contribution of central carbon metabolism to growth of E. faecalis at various sites of infection.
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spelling pubmed-82628762021-07-23 Influence of the Alternative Sigma Factor RpoN on Global Gene Expression and Carbon Catabolism in Enterococcus faecalis V583 Keffeler, Erica C. Iyer, Vijayalakshmi S. Parthasarathy, Srivatsan Ramsey, Matthew M. Gorman, Matthew J. Barke, Theresa L. Varahan, Sriram Olson, Sally Gilmore, Michael S. Abdullahi, Zakria H. Hancock, Emmaleigh N. Hancock, Lynn E. mBio Research Article The alternative sigma factor σ(54) has been shown to regulate the expression of a wide array of virulence-associated genes, as well as central metabolism, in bacterial pathogens. In Gram-positive organisms, the σ(54) is commonly associated with carbon metabolism. In this study, we show that the Enterococcus faecalis alternative sigma factor σ(54) (RpoN) and its cognate enhancer binding protein MptR are essential for mannose utilization and are primary contributors to glucose uptake through the Mpt phosphotransferase system. To gain further insight into how RpoN contributes to global transcriptional changes, we performed microarray transcriptional analysis of strain V583 and an isogenic rpoN mutant grown in a chemically defined medium with glucose as the sole carbon source. Transcripts of 340 genes were differentially affected in the rpoN mutant; the predicted functions of these genes mainly related to nutrient acquisition. These differentially expressed genes included those with predicted catabolite-responsive element (cre) sites, consistent with loss of repression by the major carbon catabolite repressor CcpA. To determine if the inability to efficiently metabolize glucose/mannose affected infection outcome, we utilized two distinct infection models. We found that the rpoN mutant is significantly attenuated in both rabbit endocarditis and murine catheter-associated urinary tract infection (CAUTI). Here, we examined a ccpA mutant in the CAUTI model and showed that the absence of carbon catabolite control also significantly attenuates bacterial tissue burden in this model. Our data highlight the contribution of central carbon metabolism to growth of E. faecalis at various sites of infection. American Society for Microbiology 2021-05-18 /pmc/articles/PMC8262876/ /pubmed/34006651 http://dx.doi.org/10.1128/mBio.00380-21 Text en Copyright © 2021 Keffeler et al. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Research Article
Keffeler, Erica C.
Iyer, Vijayalakshmi S.
Parthasarathy, Srivatsan
Ramsey, Matthew M.
Gorman, Matthew J.
Barke, Theresa L.
Varahan, Sriram
Olson, Sally
Gilmore, Michael S.
Abdullahi, Zakria H.
Hancock, Emmaleigh N.
Hancock, Lynn E.
Influence of the Alternative Sigma Factor RpoN on Global Gene Expression and Carbon Catabolism in Enterococcus faecalis V583
title Influence of the Alternative Sigma Factor RpoN on Global Gene Expression and Carbon Catabolism in Enterococcus faecalis V583
title_full Influence of the Alternative Sigma Factor RpoN on Global Gene Expression and Carbon Catabolism in Enterococcus faecalis V583
title_fullStr Influence of the Alternative Sigma Factor RpoN on Global Gene Expression and Carbon Catabolism in Enterococcus faecalis V583
title_full_unstemmed Influence of the Alternative Sigma Factor RpoN on Global Gene Expression and Carbon Catabolism in Enterococcus faecalis V583
title_short Influence of the Alternative Sigma Factor RpoN on Global Gene Expression and Carbon Catabolism in Enterococcus faecalis V583
title_sort influence of the alternative sigma factor rpon on global gene expression and carbon catabolism in enterococcus faecalis v583
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8262876/
https://www.ncbi.nlm.nih.gov/pubmed/34006651
http://dx.doi.org/10.1128/mBio.00380-21
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