Antibiotic-Driven Dysbiosis Mediates Intraluminal Agglutination and Alternative Segregation of <named-content content-type="genus-species">Enterococcus faecium</named-content> from the Intestinal Epithelium

ABSTRACT The microbiota of the mammalian gastrointestinal tract is a complex ecosystem of bacterial communities that continuously interact with the mucosal immune system. In a healthy host, the mucosal immune system maintains homeostasis in the intestine and prevents invasion of pathogenic bacteria,...

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Autores principales:	Antoni P. A. Hendrickx, Janetta Top, Jumamurat R. Bayjanov, Hans Kemperman, Malbert R. C. Rogers, Fernanda L. Paganelli, Marc J. M. Bonten, Rob J. L. Willems
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2015
Materias:	Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/d748b040e09e4a3a999ab6747c89b9ab
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spelling	oai:doaj.org-article:d748b040e09e4a3a999ab6747c89b9ab2021-11-15T15:41:23ZAntibiotic-Driven Dysbiosis Mediates Intraluminal Agglutination and Alternative Segregation of <named-content content-type="genus-species">Enterococcus faecium</named-content> from the Intestinal Epithelium10.1128/mBio.01346-152150-7511https://doaj.org/article/d748b040e09e4a3a999ab6747c89b9ab2015-12-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.01346-15https://doaj.org/toc/2150-7511ABSTRACT The microbiota of the mammalian gastrointestinal tract is a complex ecosystem of bacterial communities that continuously interact with the mucosal immune system. In a healthy host, the mucosal immune system maintains homeostasis in the intestine and prevents invasion of pathogenic bacteria, a phenomenon termed colonization resistance. Antibiotics create dysbiosis of microbiota, thereby decreasing colonization resistance and facilitating infections caused by antibiotic-resistant bacteria. Here we describe how cephalosporin antibiotics create dysbiosis in the mouse large intestine, allowing intestinal outgrowth of antimicrobial-resistant Enterococcus faecium. This is accompanied by a reduction of the mucus-associated gut microbiota layer, colon wall, and Muc-2 mucus layer. E. faecium agglutinates intraluminally in an extracellular matrix consisting of secretory IgA (sIgA), polymeric immunoglobulin receptor (pIgR), and epithelial cadherin (E-cadherin) proteins, thereby maintaining spatial segregation of E. faecium from the intestinal wall. Addition of recombinant E-cadherin and pIgR proteins or purified IgA to enterococci in vitro mimics agglutination of E. faecium in vivo. Also, the Ca2+ levels temporarily increased by 75% in feces of antibiotic-treated mice, which led to deformation of E-cadherin adherens junctions between colonic intestinal epithelial cells and release of E-cadherin as an extracellular matrix entrapping E. faecium. These findings indicate that during antibiotic-induced dysbiosis, the intestinal epithelium stays separated from an invading pathogen through an extracellular matrix in which sIgA, pIgR, and E-cadherin are colocalized. Future mucosal vaccination strategies to control E. faecium or other opportunistic pathogens may prevent multidrug-resistant infections, hospital transmission, and outbreaks. IMPORTANCE Infections with antibiotic-resistant enterococci are an emerging worldwide problem because enterococci are resistant to most of the antibiotics used in hospitals. During antibiotic treatment, the normal bacteria are replaced by resistant enterococci within the gut, from which they can spread and cause infections. We studied antibiotic-mediated intestinal proliferation of multidrug-resistant Enterococcus faecium and the effects on intestinal architecture. We demonstrated that antibiotics allow proliferation of E. faecium in the gut, alter the mucus-associated gut bacterial layer, and reduce the colon wall, mucus thickness, and amount of Muc-2 protein. E. faecium is agglutinated in the intestine in a matrix consisting of host molecules. We hypothesize that this matrix maintains a segregation of E. faecium from the epithelium. Understanding the processes that occur in the gut during antibiotic treatment may provide clues for future mucosal vaccination strategies to control E. faecium or other multidrug-resistant opportunistic pathogens, thereby preventing infections, hospital transmission, and outbreaks.Antoni P. A. HendrickxJanetta TopJumamurat R. BayjanovHans KempermanMalbert R. C. RogersFernanda L. PaganelliMarc J. M. BontenRob J. L. WillemsAmerican Society for MicrobiologyarticleMicrobiologyQR1-502ENmBio, Vol 6, Iss 6 (2015)
institution	DOAJ
collection	DOAJ
language	EN
topic	Microbiology QR1-502
spellingShingle	Microbiology QR1-502 Antoni P. A. Hendrickx Janetta Top Jumamurat R. Bayjanov Hans Kemperman Malbert R. C. Rogers Fernanda L. Paganelli Marc J. M. Bonten Rob J. L. Willems Antibiotic-Driven Dysbiosis Mediates Intraluminal Agglutination and Alternative Segregation of <named-content content-type="genus-species">Enterococcus faecium</named-content> from the Intestinal Epithelium
description	ABSTRACT The microbiota of the mammalian gastrointestinal tract is a complex ecosystem of bacterial communities that continuously interact with the mucosal immune system. In a healthy host, the mucosal immune system maintains homeostasis in the intestine and prevents invasion of pathogenic bacteria, a phenomenon termed colonization resistance. Antibiotics create dysbiosis of microbiota, thereby decreasing colonization resistance and facilitating infections caused by antibiotic-resistant bacteria. Here we describe how cephalosporin antibiotics create dysbiosis in the mouse large intestine, allowing intestinal outgrowth of antimicrobial-resistant Enterococcus faecium. This is accompanied by a reduction of the mucus-associated gut microbiota layer, colon wall, and Muc-2 mucus layer. E. faecium agglutinates intraluminally in an extracellular matrix consisting of secretory IgA (sIgA), polymeric immunoglobulin receptor (pIgR), and epithelial cadherin (E-cadherin) proteins, thereby maintaining spatial segregation of E. faecium from the intestinal wall. Addition of recombinant E-cadherin and pIgR proteins or purified IgA to enterococci in vitro mimics agglutination of E. faecium in vivo. Also, the Ca2+ levels temporarily increased by 75% in feces of antibiotic-treated mice, which led to deformation of E-cadherin adherens junctions between colonic intestinal epithelial cells and release of E-cadherin as an extracellular matrix entrapping E. faecium. These findings indicate that during antibiotic-induced dysbiosis, the intestinal epithelium stays separated from an invading pathogen through an extracellular matrix in which sIgA, pIgR, and E-cadherin are colocalized. Future mucosal vaccination strategies to control E. faecium or other opportunistic pathogens may prevent multidrug-resistant infections, hospital transmission, and outbreaks. IMPORTANCE Infections with antibiotic-resistant enterococci are an emerging worldwide problem because enterococci are resistant to most of the antibiotics used in hospitals. During antibiotic treatment, the normal bacteria are replaced by resistant enterococci within the gut, from which they can spread and cause infections. We studied antibiotic-mediated intestinal proliferation of multidrug-resistant Enterococcus faecium and the effects on intestinal architecture. We demonstrated that antibiotics allow proliferation of E. faecium in the gut, alter the mucus-associated gut bacterial layer, and reduce the colon wall, mucus thickness, and amount of Muc-2 protein. E. faecium is agglutinated in the intestine in a matrix consisting of host molecules. We hypothesize that this matrix maintains a segregation of E. faecium from the epithelium. Understanding the processes that occur in the gut during antibiotic treatment may provide clues for future mucosal vaccination strategies to control E. faecium or other multidrug-resistant opportunistic pathogens, thereby preventing infections, hospital transmission, and outbreaks.
format	article
author	Antoni P. A. Hendrickx Janetta Top Jumamurat R. Bayjanov Hans Kemperman Malbert R. C. Rogers Fernanda L. Paganelli Marc J. M. Bonten Rob J. L. Willems
author_facet	Antoni P. A. Hendrickx Janetta Top Jumamurat R. Bayjanov Hans Kemperman Malbert R. C. Rogers Fernanda L. Paganelli Marc J. M. Bonten Rob J. L. Willems
author_sort	Antoni P. A. Hendrickx
title	Antibiotic-Driven Dysbiosis Mediates Intraluminal Agglutination and Alternative Segregation of <named-content content-type="genus-species">Enterococcus faecium</named-content> from the Intestinal Epithelium
title_short	Antibiotic-Driven Dysbiosis Mediates Intraluminal Agglutination and Alternative Segregation of <named-content content-type="genus-species">Enterococcus faecium</named-content> from the Intestinal Epithelium
title_full	Antibiotic-Driven Dysbiosis Mediates Intraluminal Agglutination and Alternative Segregation of <named-content content-type="genus-species">Enterococcus faecium</named-content> from the Intestinal Epithelium
title_fullStr	Antibiotic-Driven Dysbiosis Mediates Intraluminal Agglutination and Alternative Segregation of <named-content content-type="genus-species">Enterococcus faecium</named-content> from the Intestinal Epithelium
title_full_unstemmed	Antibiotic-Driven Dysbiosis Mediates Intraluminal Agglutination and Alternative Segregation of <named-content content-type="genus-species">Enterococcus faecium</named-content> from the Intestinal Epithelium
title_sort	antibiotic-driven dysbiosis mediates intraluminal agglutination and alternative segregation of <named-content content-type="genus-species">enterococcus faecium</named-content> from the intestinal epithelium
publisher	American Society for Microbiology
publishDate	2015
url	https://doaj.org/article/d748b040e09e4a3a999ab6747c89b9ab
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Antibiotic-Driven Dysbiosis Mediates Intraluminal Agglutination and Alternative Segregation of <named-content content-type="genus-species">Enterococcus faecium</named-content> from the Intestinal Epithelium

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