Remodeling of the Intestinal Brush Border Underlies Adhesion and Virulence of an Enteric Pathogen

ABSTRACT Intestinal colonization by Vibrio parahaemolyticus—the most common cause of seafood-borne bacterial enteritis worldwide—induces extensive disruption of intestinal microvilli. In orogastrically infected infant rabbits, reorganization of the apical brush border membrane includes effacement of...

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Autores principales:	Xiaohui Zhou, Ramiro H. Massol, Fumihiko Nakamura, Xiang Chen, Benjamin E. Gewurz, Brigid M. Davis, Wayne I. Lencer, Matthew K. Waldor
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2014
Materias:	Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/25e743cca40544a18c79597f0a5ab308
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spelling	oai:doaj.org-article:25e743cca40544a18c79597f0a5ab3082021-11-15T15:47:21ZRemodeling of the Intestinal Brush Border Underlies Adhesion and Virulence of an Enteric Pathogen10.1128/mBio.01639-142150-7511https://doaj.org/article/25e743cca40544a18c79597f0a5ab3082014-08-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.01639-14https://doaj.org/toc/2150-7511ABSTRACT Intestinal colonization by Vibrio parahaemolyticus—the most common cause of seafood-borne bacterial enteritis worldwide—induces extensive disruption of intestinal microvilli. In orogastrically infected infant rabbits, reorganization of the apical brush border membrane includes effacement of some microvilli and marked elongation of others. All diarrhea, inflammation, and intestinal pathology associated with V. parahaemolyticus infection are dependent upon one of its type 3 secretion systems (T3SS2); however, translocated effectors that directly mediate brush border restructuring and bacterial adhesion are not known. Here, we demonstrate that the effector VopV is essential for V. parahaemolyticus intestinal colonization and therefore its pathogenicity, that it induces effacement of brush border microvilli, and that this effacement is required for adhesion of V. parahaemolyticus to enterocytes. VopV contains multiple functionally independent and mechanistically distinct domains through which it disrupts microvilli. We show that interaction between VopV and filamin, as well as VopV’s previously noted interaction with actin, mediates enterocyte cytoskeletal reorganization. VopV’s multipronged approach to epithelial restructuring, coupled with its impact on colonization, suggests that remodeling of the epithelial brush border is a critical step in pathogenesis. IMPORTANCE Colonization of the small bowel by Vibrio parahaemolyticus, the most common bacterial agent of seafood-borne enteric disease, induces extensive structural changes in the intestinal epithelium. Here, we show that this diarrheal pathogen’s colonization and virulence depend upon VopV, a bacterial protein that is transferred into host epithelial cells. VopV induces marked rearrangement of the apical epithelial cell membrane, including elimination of microvilli, by two means: through interaction with actin and through a previously unrecognized interaction with the actin-cross-linking protein filamin. VopV-mediated “effacement” of microvilli enables V. parahaemolyticus to adhere to host cells, although VopV may not directly mediate adhesion. VopV’s effects on microvillus structure and bacterial adhesion likely account for its essential role in V. parahaemolyticus intestinal pathogenesis. Our findings suggest a new role for filamin in brush border maintenance and raise the possibility that microvillus effacement is a common strategy among enteric pathogens for enhancing adhesion to host cells.Xiaohui ZhouRamiro H. MassolFumihiko NakamuraXiang ChenBenjamin E. GewurzBrigid M. DavisWayne I. LencerMatthew K. WaldorAmerican Society for MicrobiologyarticleMicrobiologyQR1-502ENmBio, Vol 5, Iss 4 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Microbiology QR1-502
spellingShingle	Microbiology QR1-502 Xiaohui Zhou Ramiro H. Massol Fumihiko Nakamura Xiang Chen Benjamin E. Gewurz Brigid M. Davis Wayne I. Lencer Matthew K. Waldor Remodeling of the Intestinal Brush Border Underlies Adhesion and Virulence of an Enteric Pathogen
description	ABSTRACT Intestinal colonization by Vibrio parahaemolyticus—the most common cause of seafood-borne bacterial enteritis worldwide—induces extensive disruption of intestinal microvilli. In orogastrically infected infant rabbits, reorganization of the apical brush border membrane includes effacement of some microvilli and marked elongation of others. All diarrhea, inflammation, and intestinal pathology associated with V. parahaemolyticus infection are dependent upon one of its type 3 secretion systems (T3SS2); however, translocated effectors that directly mediate brush border restructuring and bacterial adhesion are not known. Here, we demonstrate that the effector VopV is essential for V. parahaemolyticus intestinal colonization and therefore its pathogenicity, that it induces effacement of brush border microvilli, and that this effacement is required for adhesion of V. parahaemolyticus to enterocytes. VopV contains multiple functionally independent and mechanistically distinct domains through which it disrupts microvilli. We show that interaction between VopV and filamin, as well as VopV’s previously noted interaction with actin, mediates enterocyte cytoskeletal reorganization. VopV’s multipronged approach to epithelial restructuring, coupled with its impact on colonization, suggests that remodeling of the epithelial brush border is a critical step in pathogenesis. IMPORTANCE Colonization of the small bowel by Vibrio parahaemolyticus, the most common bacterial agent of seafood-borne enteric disease, induces extensive structural changes in the intestinal epithelium. Here, we show that this diarrheal pathogen’s colonization and virulence depend upon VopV, a bacterial protein that is transferred into host epithelial cells. VopV induces marked rearrangement of the apical epithelial cell membrane, including elimination of microvilli, by two means: through interaction with actin and through a previously unrecognized interaction with the actin-cross-linking protein filamin. VopV-mediated “effacement” of microvilli enables V. parahaemolyticus to adhere to host cells, although VopV may not directly mediate adhesion. VopV’s effects on microvillus structure and bacterial adhesion likely account for its essential role in V. parahaemolyticus intestinal pathogenesis. Our findings suggest a new role for filamin in brush border maintenance and raise the possibility that microvillus effacement is a common strategy among enteric pathogens for enhancing adhesion to host cells.
format	article
author	Xiaohui Zhou Ramiro H. Massol Fumihiko Nakamura Xiang Chen Benjamin E. Gewurz Brigid M. Davis Wayne I. Lencer Matthew K. Waldor
author_facet	Xiaohui Zhou Ramiro H. Massol Fumihiko Nakamura Xiang Chen Benjamin E. Gewurz Brigid M. Davis Wayne I. Lencer Matthew K. Waldor
author_sort	Xiaohui Zhou
title	Remodeling of the Intestinal Brush Border Underlies Adhesion and Virulence of an Enteric Pathogen
title_short	Remodeling of the Intestinal Brush Border Underlies Adhesion and Virulence of an Enteric Pathogen
title_full	Remodeling of the Intestinal Brush Border Underlies Adhesion and Virulence of an Enteric Pathogen
title_fullStr	Remodeling of the Intestinal Brush Border Underlies Adhesion and Virulence of an Enteric Pathogen
title_full_unstemmed	Remodeling of the Intestinal Brush Border Underlies Adhesion and Virulence of an Enteric Pathogen
title_sort	remodeling of the intestinal brush border underlies adhesion and virulence of an enteric pathogen
publisher	American Society for Microbiology
publishDate	2014
url	https://doaj.org/article/25e743cca40544a18c79597f0a5ab308
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Remodeling of the Intestinal Brush Border Underlies Adhesion and Virulence of an Enteric Pathogen

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