2005 Fiscal Year Final Research Report Summary
Molecular mimic of group A streptococcal surface proteins
| Project/Area Number |
16390525
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Morphological basic dentistry
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| Research Institution | Osaka University |
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Principal Investigator |
KAWABATA Shigetada Osaka University, Graduate School of Dentistry, Associate Professor, 大学院・歯学研究科, 助教授 (50273694)
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| Co-Investigator(Kenkyū-buntansha) |
NAKAGAWA Ichiro Tokyo University, The Institute of Medical Science, Associate Professor, 医科学研究所, 助教授 (70294113)
OKAMOTO Shigefumi Fukuoka Dental College, Faculty of Dentistry, Assistant Professor, 歯学部, 講師 (50311759)
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| Project Period (FY) |
2004 – 2005
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| Keywords | Streptococcus pyogenes / vaccine / fibronectin / invasion / antibody / collagen |
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| Research 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. Conclusion. The Fn-binding RD and N terminus of FbaA are potential vaccine candidates for M1 strains of S.pyogenes infection.
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