title: Protective immunity against Streptococcus pyogenes challenge in mice after immunization with fibronectin-binding protein.
abstract: BACKGROUND
  Surface-associated fibronectin (Fn)-binding proteins of Streptococcus pyogenes play an important role in the bacterial invasion of epithelial cells. We examined the functional domain and protective antigenicity of the Fn-binding protein FbaA.
  
  
  METHODS
  To investigate the functional domain of FbaA and its localization on S. pyogenes, a series of recombinant glutathione S-transferase (GST)-truncated FbaA proteins was used for immunofluorescent microscopy, ligand blotting, and Biacore analyses. Mice were immunized with the truncated proteins for the determination of the immunogenic domains that contribute to protection against S. pyogenes infection.
  
  
  RESULTS
  Ligand-blotting and Biacore analyses revealed that the FbaA fragments harboring a proline-rich repeat domain (RD), but not the N- and C-terminal regions, possessed Fn-binding activity. Immunofluorescent microscopy findings showed that the N terminus and RD were exposed to external regions, which suggests that the RD serves as a Fn-binding element on live organisms. Specific antibodies were efficiently induced in N terminus- and RD-immunized mice and demonstrated bactericidal activity against S. pyogenes in vitro. FbaA-immunized mice survived significantly longer than GST-immunized mice after infection with serotype M1 and M49 strains expressing FbaA.
  
  
  CONCLUSIONS
  The Fn-binding RD and N terminus of FbaA are potential vaccine candidates for M1 strains of S. pyogenes infection.
authors.affiliation: Department of Oral and Molecular Microbiology, Osaka University Graduate School of Dentistry, Japan.
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Terao
authors.forename: Shigefumi
authors.initials: S
authors.lastname: Okamoto
authors.forename: Kosuke
authors.initials: K
authors.lastname: Kataoka
authors.forename: Shigeyuki
authors.initials: S
authors.lastname: Hamada
authors.forename: Shigetada
authors.initials: S
authors.lastname: Kawabata
mesh_terms: D018829:Adhesins, Bacterial / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood / Q000276:immunology; D000954:Antigens, Surface / Q000032:analysis; D026481:Blotting, Far-Western; D004195:Disease Models, Animal; D051379:Mice; D008856:Microscopy, Fluorescence; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D017384:Sequence Deletion; D013290:Streptococcal Infections / Q000276:immunology / Q000517:prevention & control*; D013297:Streptococcus pyogenes / Q000737:chemistry / Q000276:immunology*; D016019:Survival Analysis
chemical_list: D018829:Adhesins, Bacterial; D000907:Antibodies, Bacterial; D000954:Antigens, Surface; C078635:fibronectin-binding proteins, bacterial