title: 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 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.
  
  
  OBJECTIVE
  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.
authors.affiliation: Division of Infectious Diseases, Brigham and Women's Hospital, Boston, Massachusetts, USA Department of Microbiology and Immunobiology, Harvard Medical School, Boston, Massachusetts, USA HHMI, Boston, Massachusetts, USA Department of Pathobiology and Veterinary Science, University of Connecticut, Storrs, Connecticut, USA.
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Zhou
authors.forename: Ramiro H
authors.initials: RH
authors.lastname: Massol
authors.affiliation: Translational Medicine Division, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA.
authors.forename: Fumihiko
authors.initials: F
authors.lastname: Nakamura
authors.affiliation: Division of Infectious Diseases, Brigham and Women's Hospital, Boston, Massachusetts, USA Department of Microbiology and Immunobiology, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Xiang
authors.initials: X
authors.lastname: Chen
authors.forename: Benjamin E
authors.initials: BE
authors.lastname: Gewurz
authors.forename: Brigid M
authors.initials: BM
authors.lastname: Davis
authors.forename: Wayne I
authors.initials: WI
authors.lastname: Lencer
authors.affiliation: MWaldor@research.bwh.harvard.edu.
authors.forename: Matthew K
authors.initials: MK
authors.lastname: Waldor
mesh_terms: D000818:Animals; D001422:Bacterial Adhesion; D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D004751:Enteritis / Q000382:microbiology; D064448:Filamins / Q000378:metabolism; D054884:Host-Pathogen Interactions; D007413:Intestinal Mucosa / Q000382:microbiology* / Q000648:ultrastructure*; D008871:Microvilli / Q000648:ultrastructure*; D011817:Rabbits; D014736:Vibrio parahaemolyticus / Q000472:pathogenicity* / Q000502:physiology*; D014774:Virulence; D037521:Virulence Factors / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D064448:Filamins; D037521:Virulence Factors