A Giant Extracellular Matrix Binding Protein of <italic toggle="yes">Staphylococcus epidermidis</italic> Binds Surface-Immobilized Fibronectin via a Novel Mechanism

ABSTRACT Although it is normally an innocuous part of the human skin microbiota, Staphylococcus epidermidis has emerged as a major nosocomial pathogen, and implanted foreign materials are an essential risk factor for the development of an infection. The extraordinary efficiency of S. epidermidis to...

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Autores principales:	Henning Büttner, Markus Perbandt, Thomas Kohler, Alexey Kikhney, Manuel Wolters, Martin Christner, Marisol Heise, Jérôme Wilde, Samira Weißelberg, Anna Both, Christian Betzel, Sven Hammerschmidt, Dmitri Svergun, Martin Aepfelbacher, Holger Rohde
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Lenguaje:	EN
Publicado:	American Society for Microbiology 2020
Materias:	Staphylococcus biofilms fibronectin binding surface proteins surface structures Microbiology QR1-502
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spelling	oai:doaj.org-article:df62cb30d16a46af8905316d3633a8082021-11-15T16:19:08ZA Giant Extracellular Matrix Binding Protein of <italic toggle="yes">Staphylococcus epidermidis</italic> Binds Surface-Immobilized Fibronectin via a Novel Mechanism10.1128/mBio.01612-202150-7511https://doaj.org/article/df62cb30d16a46af8905316d3633a8082020-10-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.01612-20https://doaj.org/toc/2150-7511ABSTRACT Although it is normally an innocuous part of the human skin microbiota, Staphylococcus epidermidis has emerged as a major nosocomial pathogen, and implanted foreign materials are an essential risk factor for the development of an infection. The extraordinary efficiency of S. epidermidis to colonize artificial surfaces is particularly related to the ability to form biofilms. Biofilm formation itself critically depends on stable pathogen binding to extracellular host matrix components, e.g. fibronectin (Fn), covering inserted devices in vast amounts. Extracellular matrix binding protein (Embp) and its subdomains referred to as the F-repeat and the FG-repeat are critical for adherence of S. epidermidis to surface-immobilized Fn. Embp-Fn interactions preferentially occur with surface-bound, but not folded, globular Fn via binding to the F3 domain. High-resolution structure analysis of F- and FG-repeats revealed that both repeats are composed of two tightly connected triple α-helix bundles, exhibiting an elongated but rather rigid structural organization in solution. Both F- and FG-repeat possess Fn-binding capacity via interactions with type III subdomain FN12, involving residues within the C and F β-sheet. FN12 essentially supports stability of the globular Fn state, and thus these findings reasonably explain why Embp-mediated interaction of S. epidermidis necessitates Fn surface immobilization. Thus, Embp employs an uncharacterized bacterial Fn-binding mechanism to promote staphylococcal adherence. IMPORTANCE Staphylococcus epidermidis is a leading pathogen in implant-associated hospital infections. The pathogenesis critically depends on bacterial binding to ECM components, specifically fibronectin (Fn). The cell surface-localized, 1-MDa extracellular matrix binding protein (Embp) is essentially characterized by 10 F- and 40 FG-repeats. These repetitive units, each characterized by two α-helical bundles, organize themselves in a rigid, elongated form. Embp binds preferentially to surface-localized but not soluble Fn, with both F- and FG-repeats being sufficient for Fn binding and resulting bacterial adherence. Binding preferentially involves Fn type III domain, specifically residues of FN12 β-sheets C and F. Both play key role in stabilizing the globular Fn conformation, explaining the necessity of Fn surface immobilization for a subsequent interaction with Embp. In comparison to many other bacterial Fn-binding proteins using the Fn N terminus, Embp employs a previously undescribed mechanism supporting the adhesion of S. epidermidis to surface-immobilized Fn.Henning BüttnerMarkus PerbandtThomas KohlerAlexey KikhneyManuel WoltersMartin ChristnerMarisol HeiseJérôme WildeSamira WeißelbergAnna BothChristian BetzelSven HammerschmidtDmitri SvergunMartin AepfelbacherHolger RohdeAmerican Society for MicrobiologyarticleStaphylococcusbiofilmsfibronectin bindingsurface proteinssurface structuresMicrobiologyQR1-502ENmBio, Vol 11, Iss 5 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	Staphylococcus biofilms fibronectin binding surface proteins surface structures Microbiology QR1-502
spellingShingle	Staphylococcus biofilms fibronectin binding surface proteins surface structures Microbiology QR1-502 Henning Büttner Markus Perbandt Thomas Kohler Alexey Kikhney Manuel Wolters Martin Christner Marisol Heise Jérôme Wilde Samira Weißelberg Anna Both Christian Betzel Sven Hammerschmidt Dmitri Svergun Martin Aepfelbacher Holger Rohde A Giant Extracellular Matrix Binding Protein of <italic toggle="yes">Staphylococcus epidermidis</italic> Binds Surface-Immobilized Fibronectin via a Novel Mechanism
description	ABSTRACT Although it is normally an innocuous part of the human skin microbiota, Staphylococcus epidermidis has emerged as a major nosocomial pathogen, and implanted foreign materials are an essential risk factor for the development of an infection. The extraordinary efficiency of S. epidermidis to colonize artificial surfaces is particularly related to the ability to form biofilms. Biofilm formation itself critically depends on stable pathogen binding to extracellular host matrix components, e.g. fibronectin (Fn), covering inserted devices in vast amounts. Extracellular matrix binding protein (Embp) and its subdomains referred to as the F-repeat and the FG-repeat are critical for adherence of S. epidermidis to surface-immobilized Fn. Embp-Fn interactions preferentially occur with surface-bound, but not folded, globular Fn via binding to the F3 domain. High-resolution structure analysis of F- and FG-repeats revealed that both repeats are composed of two tightly connected triple α-helix bundles, exhibiting an elongated but rather rigid structural organization in solution. Both F- and FG-repeat possess Fn-binding capacity via interactions with type III subdomain FN12, involving residues within the C and F β-sheet. FN12 essentially supports stability of the globular Fn state, and thus these findings reasonably explain why Embp-mediated interaction of S. epidermidis necessitates Fn surface immobilization. Thus, Embp employs an uncharacterized bacterial Fn-binding mechanism to promote staphylococcal adherence. IMPORTANCE Staphylococcus epidermidis is a leading pathogen in implant-associated hospital infections. The pathogenesis critically depends on bacterial binding to ECM components, specifically fibronectin (Fn). The cell surface-localized, 1-MDa extracellular matrix binding protein (Embp) is essentially characterized by 10 F- and 40 FG-repeats. These repetitive units, each characterized by two α-helical bundles, organize themselves in a rigid, elongated form. Embp binds preferentially to surface-localized but not soluble Fn, with both F- and FG-repeats being sufficient for Fn binding and resulting bacterial adherence. Binding preferentially involves Fn type III domain, specifically residues of FN12 β-sheets C and F. Both play key role in stabilizing the globular Fn conformation, explaining the necessity of Fn surface immobilization for a subsequent interaction with Embp. In comparison to many other bacterial Fn-binding proteins using the Fn N terminus, Embp employs a previously undescribed mechanism supporting the adhesion of S. epidermidis to surface-immobilized Fn.
format	article
author	Henning Büttner Markus Perbandt Thomas Kohler Alexey Kikhney Manuel Wolters Martin Christner Marisol Heise Jérôme Wilde Samira Weißelberg Anna Both Christian Betzel Sven Hammerschmidt Dmitri Svergun Martin Aepfelbacher Holger Rohde
author_facet	Henning Büttner Markus Perbandt Thomas Kohler Alexey Kikhney Manuel Wolters Martin Christner Marisol Heise Jérôme Wilde Samira Weißelberg Anna Both Christian Betzel Sven Hammerschmidt Dmitri Svergun Martin Aepfelbacher Holger Rohde
author_sort	Henning Büttner
title	A Giant Extracellular Matrix Binding Protein of <italic toggle="yes">Staphylococcus epidermidis</italic> Binds Surface-Immobilized Fibronectin via a Novel Mechanism
title_short	A Giant Extracellular Matrix Binding Protein of <italic toggle="yes">Staphylococcus epidermidis</italic> Binds Surface-Immobilized Fibronectin via a Novel Mechanism
title_full	A Giant Extracellular Matrix Binding Protein of <italic toggle="yes">Staphylococcus epidermidis</italic> Binds Surface-Immobilized Fibronectin via a Novel Mechanism
title_fullStr	A Giant Extracellular Matrix Binding Protein of <italic toggle="yes">Staphylococcus epidermidis</italic> Binds Surface-Immobilized Fibronectin via a Novel Mechanism
title_full_unstemmed	A Giant Extracellular Matrix Binding Protein of <italic toggle="yes">Staphylococcus epidermidis</italic> Binds Surface-Immobilized Fibronectin via a Novel Mechanism
title_sort	giant extracellular matrix binding protein of <italic toggle="yes">staphylococcus epidermidis</italic> binds surface-immobilized fibronectin via a novel mechanism
publisher	American Society for Microbiology
publishDate	2020
url	https://doaj.org/article/df62cb30d16a46af8905316d3633a808
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A Giant Extracellular Matrix Binding Protein of <italic toggle="yes">Staphylococcus epidermidis</italic> Binds Surface-Immobilized Fibronectin via a Novel Mechanism

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