title: Fibronectin facilitates the invasion of Orientia tsutsugamushi into host cells through interaction with a 56-kDa type-specific antigen.
abstract: BACKGROUND
  Orientia tsutsugamushi, the causative agent of scrub typhus, is an obligate intracellular bacterium. The pathogen's mechanism of cellular invasion is poorly characterized.
  
  
  METHODS
  Through ligand immunoblots, glutathione S-transferase (GST) pull-down assays, and in vitro inhibition assays of intracellular invasion, a bacterial ligand was identified and was shown to interact with fibronectin (Fn) to enhance the intracellular invasion of O. tsutsugamushi.
  
  
  RESULTS
  O. tsutsugamushi can bind to immobilized Fn in vitro, and exogenous Fn stimulates bacterial invasion of mammalian host cells. Bacterial invasion in the presence of Fn was abrogated by the addition of Arg-Gly-Asp peptides or by an anti-alpha5beta1 integrin antibody. Through a ligand immunoblot and GST pull-down assay, a 56-kDa type-specific antigen (TSA56) was identified as the bacterial ligand responsible for the interaction with Fn. Antigenic domain III and the adjacent C-terminal region (aa 243-349) of TSA56 interacted with Fn. Furthermore, we found that the enhanced invasion of the pathogen was abrogated by the addition of purified recombinant peptides derived from TSA56.
  
  
  CONCLUSIONS
  Fn facilitates the invasion of O. tsutsugamushi through its interaction with TSA56.
authors.affiliation: Department of Microbiology and Immunology, Seoul National University College of Medicine, Seoul, Republic of Korea.
authors.forename: Jung-Hee
authors.initials: JH
authors.lastname: Lee
authors.forename: Nam-Hyuk
authors.initials: NH
authors.lastname: Cho
authors.forename: Se-Yoon
authors.initials: SY
authors.lastname: Kim
authors.forename: Sun-Young
authors.initials: SY
authors.lastname: Bang
authors.forename: Hyuk
authors.initials: H
authors.lastname: Chu
authors.forename: Myung-Sik
authors.initials: MS
authors.lastname: Choi
authors.forename: Ik-Sang
authors.initials: IS
authors.lastname: Kim
mesh_terms: D000818:Animals; D000942:Antigens, Bacterial / Q000502:physiology*; D001422:Bacterial Adhesion / Q000502:physiology*; D001665:Binding Sites; D002455:Cell Division; D005353:Fibronectins / Q000502:physiology*; D005982:Glutathione Transferase / Q000378:metabolism; D006801:Humans; D007739:L Cells; D051379:Mice; D012285:Orientia tsutsugamushi / Q000472:pathogenicity*; D011994:Recombinant Proteins / Q000378:metabolism; D012710:Serum Albumin, Bovine / Q000502:physiology
chemical_list: D000942:Antigens, Bacterial; D005353:Fibronectins; D011994:Recombinant Proteins; D012710:Serum Albumin, Bovine; D005982:Glutathione Transferase