NsrR, GadE, and GadX Interplay in Repressing Expression of the Escherichia coli O157:H7 LEE Pathogenicity Island in Response to Nitric Oxide

NsrR, GadE, and GadX Interplay in Repressing Expression of the Escherichia coli O157:H7 LEE Pathogenicity Island in Response to Nitric Oxide

Expression of genes of the locus of enterocyte effacement (LEE) is essential for adherence of enterohemorrhagic Escherichia coli (EHEC) to intestinal epithelial cells. Gut factors that may modulate LEE gene expression may therefore influence the outcome of the infection. Because nitric oxide (NO) is...

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Main Authors: Branchu, Priscilla, Matrat, Stéphanie, Vareille, Marjolaine, Garrivier, Annie, Durand, Alexandra, Crépin, Sébastien, Harel, Josée, Jubelin, Grégory, Gobert, Alain P.
Format: Online
Language:English
Published: Public Library of Science 2014
Online Access:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3887101/
id pubmed-3887101
recordtype oai_dc
spelling pubmed-38871012014-01-10 NsrR, GadE, and GadX Interplay in Repressing Expression of the Escherichia coli O157:H7 LEE Pathogenicity Island in Response to Nitric Oxide Branchu, Priscilla Matrat, Stéphanie Vareille, Marjolaine Garrivier, Annie Durand, Alexandra Crépin, Sébastien Harel, Josée Jubelin, Grégory Gobert, Alain P. Research Article Expression of genes of the locus of enterocyte effacement (LEE) is essential for adherence of enterohemorrhagic Escherichia coli (EHEC) to intestinal epithelial cells. Gut factors that may modulate LEE gene expression may therefore influence the outcome of the infection. Because nitric oxide (NO) is a critical effector of the intestinal immune response that may induce transcriptional regulation in enterobacteria, we investigated its influence on LEE expression in EHEC O157:H7. We demonstrate that NO inhibits the expression of genes belonging to LEE1, LEE4, and LEE5 operons, and that the NO sensor nitrite-sensitive repressor (NsrR) is a positive regulator of these operons by interacting directly with the RNA polymerase complex. In the presence of NO, NsrR detaches from the LEE1/4/5 promoter regions and does not activate transcription. In parallel, two regulators of the acid resistance pathway, GadE and GadX, are induced by NO through an indirect NsrR-dependent mechanism. In this context, we show that the NO-dependent LEE1 down-regulation is due to absence of NsrR-mediated activation and to the repressor effect of GadX. Moreover, the inhibition of expression of LEE4 and LEE5 by NO is due to loss of NsrR-mediated activation, to LEE1 down-regulation and to GadE up-regulation. Lastly, we establish that chemical or cellular sources of NO inhibit the adherence of EHEC to human intestinal epithelial cells. These results highlight the critical effect of NsrR in the regulation of the LEE pathogenicity island and the potential role of NO in the limitation of colonization by EHEC. Public Library of Science 2014-01-09 /pmc/articles/PMC3887101/ /pubmed/24415940 http://dx.doi.org/10.1371/journal.ppat.1003874 Text en © 2014 Branchu 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.
repository_type Open Access Journal
institution_category Foreign Institution
institution US National Center for Biotechnology Information
building NCBI PubMed
collection Online Access
language English
format Online
author Branchu, Priscilla
Matrat, Stéphanie
Vareille, Marjolaine
Garrivier, Annie
Durand, Alexandra
Crépin, Sébastien
Harel, Josée
Jubelin, Grégory
Gobert, Alain P.
spellingShingle Branchu, Priscilla
Matrat, Stéphanie
Vareille, Marjolaine
Garrivier, Annie
Durand, Alexandra
Crépin, Sébastien
Harel, Josée
Jubelin, Grégory
Gobert, Alain P.
NsrR, GadE, and GadX Interplay in Repressing Expression of the Escherichia coli O157:H7 LEE Pathogenicity Island in Response to Nitric Oxide
author_facet Branchu, Priscilla
Matrat, Stéphanie
Vareille, Marjolaine
Garrivier, Annie
Durand, Alexandra
Crépin, Sébastien
Harel, Josée
Jubelin, Grégory
Gobert, Alain P.
author_sort Branchu, Priscilla
title NsrR, GadE, and GadX Interplay in Repressing Expression of the Escherichia coli O157:H7 LEE Pathogenicity Island in Response to Nitric Oxide
title_short NsrR, GadE, and GadX Interplay in Repressing Expression of the Escherichia coli O157:H7 LEE Pathogenicity Island in Response to Nitric Oxide
title_full NsrR, GadE, and GadX Interplay in Repressing Expression of the Escherichia coli O157:H7 LEE Pathogenicity Island in Response to Nitric Oxide
title_fullStr NsrR, GadE, and GadX Interplay in Repressing Expression of the Escherichia coli O157:H7 LEE Pathogenicity Island in Response to Nitric Oxide
title_full_unstemmed NsrR, GadE, and GadX Interplay in Repressing Expression of the Escherichia coli O157:H7 LEE Pathogenicity Island in Response to Nitric Oxide
title_sort nsrr, gade, and gadx interplay in repressing expression of the escherichia coli o157:h7 lee pathogenicity island in response to nitric oxide
description Expression of genes of the locus of enterocyte effacement (LEE) is essential for adherence of enterohemorrhagic Escherichia coli (EHEC) to intestinal epithelial cells. Gut factors that may modulate LEE gene expression may therefore influence the outcome of the infection. Because nitric oxide (NO) is a critical effector of the intestinal immune response that may induce transcriptional regulation in enterobacteria, we investigated its influence on LEE expression in EHEC O157:H7. We demonstrate that NO inhibits the expression of genes belonging to LEE1, LEE4, and LEE5 operons, and that the NO sensor nitrite-sensitive repressor (NsrR) is a positive regulator of these operons by interacting directly with the RNA polymerase complex. In the presence of NO, NsrR detaches from the LEE1/4/5 promoter regions and does not activate transcription. In parallel, two regulators of the acid resistance pathway, GadE and GadX, are induced by NO through an indirect NsrR-dependent mechanism. In this context, we show that the NO-dependent LEE1 down-regulation is due to absence of NsrR-mediated activation and to the repressor effect of GadX. Moreover, the inhibition of expression of LEE4 and LEE5 by NO is due to loss of NsrR-mediated activation, to LEE1 down-regulation and to GadE up-regulation. Lastly, we establish that chemical or cellular sources of NO inhibit the adherence of EHEC to human intestinal epithelial cells. These results highlight the critical effect of NsrR in the regulation of the LEE pathogenicity island and the potential role of NO in the limitation of colonization by EHEC.
publisher Public Library of Science
publishDate 2014
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3887101/
_version_ 1612046267556298752

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