Flagellin hypervariable region determines symbiotic properties of commensal Escherichia coli strains

Escherichia coli represents a classical intestinal gram-negative commensal. Despite this commensalism, different E. coli strains can mediate disparate immunogenic properties in a given host. Symbiotic E. coli strains such as E. coli Nissle 1917 (EcN) are attributed beneficial properties, e.g., promo...

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Veröffentlicht in:PLoS biology 2019-06, Vol.17 (6), p.e3000334-e3000334
Hauptverfasser: Steimle, Alex, Menz, Sarah, Bender, Annika, Ball, Brianna, Weber, Alexander N R, Hagemann, Thomas, Lange, Anna, Maerz, Jan K, Parusel, Raphael, Michaelis, Lena, Schäfer, Andrea, Yao, Hans, Löw, Hanna-Christine, Beier, Sina, Tesfazgi Mebrhatu, Mehari, Gronbach, Kerstin, Wagner, Samuel, Voehringer, David, Schaller, Martin, Fehrenbacher, Birgit, Autenrieth, Ingo B, Oelschlaeger, Tobias A, Frick, Julia-Stefanie
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container_issue 6
container_start_page e3000334
container_title PLoS biology
container_volume 17
creator Steimle, Alex
Menz, Sarah
Bender, Annika
Ball, Brianna
Weber, Alexander N R
Hagemann, Thomas
Lange, Anna
Maerz, Jan K
Parusel, Raphael
Michaelis, Lena
Schäfer, Andrea
Yao, Hans
Löw, Hanna-Christine
Beier, Sina
Tesfazgi Mebrhatu, Mehari
Gronbach, Kerstin
Wagner, Samuel
Voehringer, David
Schaller, Martin
Fehrenbacher, Birgit
Autenrieth, Ingo B
Oelschlaeger, Tobias A
Frick, Julia-Stefanie
description Escherichia coli represents a classical intestinal gram-negative commensal. Despite this commensalism, different E. coli strains can mediate disparate immunogenic properties in a given host. Symbiotic E. coli strains such as E. coli Nissle 1917 (EcN) are attributed beneficial properties, e.g., promotion of intestinal homeostasis. Therefore, we aimed to identify molecular features derived from symbiotic bacteria that might help to develop innovative therapeutic alternatives for the treatment of intestinal immune disorders. This study was performed using the dextran sodium sulphate (DSS)-induced colitis mouse model, which is routinely used to evaluate potential therapeutics for the treatment of Inflammatory Bowel Diseases (IBDs). We focused on the analysis of flagellin structures of different E. coli strains. EcN flagellin was found to harbor a substantially longer hypervariable region (HVR) compared to other commensal E. coli strains, and this longer HVR mediated symbiotic properties through stronger activation of Toll-like receptor (TLR)5, thereby resulting in interleukin (IL)-22-mediated protection of mice against DSS-induced colitis. Furthermore, using bone-marrow-chimeric mice (BMCM), CD11c+ cells of the colonic lamina propria (LP) were identified as the main mediators of these flagellin-induced symbiotic effects. We propose flagellin from symbiotic E. coli strains as a potential therapeutic to restore intestinal immune homeostasis, e.g., for the treatment of IBD patients.
doi_str_mv 10.1371/journal.pbio.3000334
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Despite this commensalism, different E. coli strains can mediate disparate immunogenic properties in a given host. Symbiotic E. coli strains such as E. coli Nissle 1917 (EcN) are attributed beneficial properties, e.g., promotion of intestinal homeostasis. Therefore, we aimed to identify molecular features derived from symbiotic bacteria that might help to develop innovative therapeutic alternatives for the treatment of intestinal immune disorders. This study was performed using the dextran sodium sulphate (DSS)-induced colitis mouse model, which is routinely used to evaluate potential therapeutics for the treatment of Inflammatory Bowel Diseases (IBDs). We focused on the analysis of flagellin structures of different E. coli strains. EcN flagellin was found to harbor a substantially longer hypervariable region (HVR) compared to other commensal E. coli strains, and this longer HVR mediated symbiotic properties through stronger activation of Toll-like receptor (TLR)5, thereby resulting in interleukin (IL)-22-mediated protection of mice against DSS-induced colitis. Furthermore, using bone-marrow-chimeric mice (BMCM), CD11c+ cells of the colonic lamina propria (LP) were identified as the main mediators of these flagellin-induced symbiotic effects. 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chemically induced</topic><topic>Colitis - immunology</topic><topic>Commensalism</topic><topic>Cytokines</topic><topic>Dendritic cells</topic><topic>Dermatology</topic><topic>Dextran</topic><topic>Disease Models, Animal</topic><topic>E coli</topic><topic>Ecology and Environmental Sciences</topic><topic>Escherichia coli</topic><topic>Escherichia coli - genetics</topic><topic>Escherichia coli - metabolism</topic><topic>Escherichia coli Infections - microbiology</topic><topic>Escherichia coli Proteins - genetics</topic><topic>Female</topic><topic>Flagellin</topic><topic>Flagellin - genetics</topic><topic>Flagellin - metabolism</topic><topic>Homeostasis</topic><topic>Hospitals</topic><topic>Hygiene</topic><topic>Immune system</topic><topic>Immunogenicity</topic><topic>Infections</topic><topic>Inflammatory bowel disease</topic><topic>Inflammatory bowel diseases</topic><topic>Interleukins</topic><topic>Intestinal Mucosa</topic><topic>Intestine</topic><topic>Intestines</topic><topic>Lamina propria</topic><topic>Male</topic><topic>Medical innovations</topic><topic>Medical treatment</topic><topic>Medicine and Health Sciences</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Microbiota</topic><topic>Neutrophils</topic><topic>Physiological aspects</topic><topic>Properties (attributes)</topic><topic>Proteins</topic><topic>Research and Analysis Methods</topic><topic>Signal Transduction - immunology</topic><topic>Sodium</topic><topic>Sodium sulfate</topic><topic>Strains (organisms)</topic><topic>Supervision</topic><topic>Symbiosis - genetics</topic><topic>Symbiosis - physiology</topic><topic>Toll-Like Receptor 5 - metabolism</topic><topic>Toll-like receptors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Steimle, Alex</creatorcontrib><creatorcontrib>Menz, Sarah</creatorcontrib><creatorcontrib>Bender, Annika</creatorcontrib><creatorcontrib>Ball, Brianna</creatorcontrib><creatorcontrib>Weber, Alexander N R</creatorcontrib><creatorcontrib>Hagemann, Thomas</creatorcontrib><creatorcontrib>Lange, Anna</creatorcontrib><creatorcontrib>Maerz, Jan K</creatorcontrib><creatorcontrib>Parusel, Raphael</creatorcontrib><creatorcontrib>Michaelis, Lena</creatorcontrib><creatorcontrib>Schäfer, Andrea</creatorcontrib><creatorcontrib>Yao, Hans</creatorcontrib><creatorcontrib>Löw, Hanna-Christine</creatorcontrib><creatorcontrib>Beier, Sina</creatorcontrib><creatorcontrib>Tesfazgi Mebrhatu, Mehari</creatorcontrib><creatorcontrib>Gronbach, Kerstin</creatorcontrib><creatorcontrib>Wagner, Samuel</creatorcontrib><creatorcontrib>Voehringer, David</creatorcontrib><creatorcontrib>Schaller, Martin</creatorcontrib><creatorcontrib>Fehrenbacher, Birgit</creatorcontrib><creatorcontrib>Autenrieth, Ingo B</creatorcontrib><creatorcontrib>Oelschlaeger, Tobias A</creatorcontrib><creatorcontrib>Frick, Julia-Stefanie</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Gale In Context: Opposing Viewpoints</collection><collection>Gale In Context: Canada</collection><collection>Gale In Context: Science</collection><collection>ProQuest Central (Corporate)</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Health &amp; Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central UK/Ireland</collection><collection>Agricultural &amp; Environmental Science Collection</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health &amp; Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health &amp; Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biological Science Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Environmental Science Database</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>Environmental Science Collection</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><collection>PLoS Biology</collection><jtitle>PLoS biology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Steimle, Alex</au><au>Menz, Sarah</au><au>Bender, Annika</au><au>Ball, Brianna</au><au>Weber, Alexander N R</au><au>Hagemann, Thomas</au><au>Lange, Anna</au><au>Maerz, Jan K</au><au>Parusel, Raphael</au><au>Michaelis, Lena</au><au>Schäfer, Andrea</au><au>Yao, Hans</au><au>Löw, Hanna-Christine</au><au>Beier, Sina</au><au>Tesfazgi Mebrhatu, Mehari</au><au>Gronbach, Kerstin</au><au>Wagner, Samuel</au><au>Voehringer, David</au><au>Schaller, Martin</au><au>Fehrenbacher, Birgit</au><au>Autenrieth, Ingo B</au><au>Oelschlaeger, Tobias A</au><au>Frick, Julia-Stefanie</au><au>Teixeira, Luis</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Flagellin hypervariable region determines symbiotic properties of commensal Escherichia coli strains</atitle><jtitle>PLoS biology</jtitle><addtitle>PLoS Biol</addtitle><date>2019-06-17</date><risdate>2019</risdate><volume>17</volume><issue>6</issue><spage>e3000334</spage><epage>e3000334</epage><pages>e3000334-e3000334</pages><issn>1545-7885</issn><issn>1544-9173</issn><eissn>1545-7885</eissn><abstract>Escherichia coli represents a classical intestinal gram-negative commensal. Despite this commensalism, different E. coli strains can mediate disparate immunogenic properties in a given host. Symbiotic E. coli strains such as E. coli Nissle 1917 (EcN) are attributed beneficial properties, e.g., promotion of intestinal homeostasis. Therefore, we aimed to identify molecular features derived from symbiotic bacteria that might help to develop innovative therapeutic alternatives for the treatment of intestinal immune disorders. This study was performed using the dextran sodium sulphate (DSS)-induced colitis mouse model, which is routinely used to evaluate potential therapeutics for the treatment of Inflammatory Bowel Diseases (IBDs). We focused on the analysis of flagellin structures of different E. coli strains. EcN flagellin was found to harbor a substantially longer hypervariable region (HVR) compared to other commensal E. coli strains, and this longer HVR mediated symbiotic properties through stronger activation of Toll-like receptor (TLR)5, thereby resulting in interleukin (IL)-22-mediated protection of mice against DSS-induced colitis. Furthermore, using bone-marrow-chimeric mice (BMCM), CD11c+ cells of the colonic lamina propria (LP) were identified as the main mediators of these flagellin-induced symbiotic effects. We propose flagellin from symbiotic E. coli strains as a potential therapeutic to restore intestinal immune homeostasis, e.g., for the treatment of IBD patients.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>31206517</pmid><doi>10.1371/journal.pbio.3000334</doi><orcidid>https://orcid.org/0000-0003-1808-3556</orcidid><orcidid>https://orcid.org/0000-0002-2532-1922</orcidid><orcidid>https://orcid.org/0000-0001-8157-162X</orcidid><orcidid>https://orcid.org/0000-0002-8230-4256</orcidid><orcidid>https://orcid.org/0000-0002-7662-7956</orcidid><oa>free_for_read</oa></addata></record>
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identifier ISSN: 1545-7885
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issn 1545-7885
1544-9173
1545-7885
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subjects Animals
Bacteria
Biology and Life Sciences
Bone marrow
Border patrol
CD11c antigen
Colitis
Colitis - chemically induced
Colitis - immunology
Commensalism
Cytokines
Dendritic cells
Dermatology
Dextran
Disease Models, Animal
E coli
Ecology and Environmental Sciences
Escherichia coli
Escherichia coli - genetics
Escherichia coli - metabolism
Escherichia coli Infections - microbiology
Escherichia coli Proteins - genetics
Female
Flagellin
Flagellin - genetics
Flagellin - metabolism
Homeostasis
Hospitals
Hygiene
Immune system
Immunogenicity
Infections
Inflammatory bowel disease
Inflammatory bowel diseases
Interleukins
Intestinal Mucosa
Intestine
Intestines
Lamina propria
Male
Medical innovations
Medical treatment
Medicine and Health Sciences
Mice
Mice, Inbred C57BL
Microbiota
Neutrophils
Physiological aspects
Properties (attributes)
Proteins
Research and Analysis Methods
Signal Transduction - immunology
Sodium
Sodium sulfate
Strains (organisms)
Supervision
Symbiosis - genetics
Symbiosis - physiology
Toll-Like Receptor 5 - metabolism
Toll-like receptors
title Flagellin hypervariable region determines symbiotic properties of commensal Escherichia coli strains
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