The identification of cell surface antigen of oral streptococcus for development of vaccine for oral cancer

• Project/Area Number: 22592046
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Morphological basic dentistry
• Research Institution: Iwate Medical University
• Principal Investigator: SASAKI Minoru 岩手医科大学, 歯学部, 准教授 (40187133)
• Co-Investigator(Renkei-kenkyūsha): KIMURA Shigenobu 岩手医科大学, 歯学部, 教授 (10177917) ; SHIMOYAMA Yu 岩手医科大学, 歯学部, 助教 (90453331)
• Project Period (FY): 2010 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2012: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000); Fiscal Year 2011: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000); Fiscal Year 2010: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
• Keywords: Streptococcus anginosus / フィブロネクチン結合タンパク質 / 上皮細胞 / 付着因子 / S. anginosus / 口腔レンサ球菌 / 口腔癌 / ワクチン開発 / 粘膜上皮細胞 / 付着

Research Abstract

Streptococcus anginosus inhabits dental plaques, and its infection in oral mucosa could be closely related with some squamous cell carcinoma. In this study for the development of vaccine, the fibronectin binding protein gene of S. anginosus, designated fbp62 was cloned, and the pathogenic involvement of Fbp62 in S. anginosusinfection was investigated. The results indicated that the adhesive ability of an fbp62knockout mutan t (Dfbp62) of S. anginosus to mucosal epithelial cells diminished significantly, and that the Dfbp62-infected mice showed considerably lower mortality and abscess formation rates, compared to the wild type S. anginosus-infected mice. Thus, a novel fibronectin binding protein of S. anginosus, Fbp62, could be an effective vaccine candidate for the S. anginosus-related oral cancer.

Research Products

• [Journal Article] Subcutaneous tissue reactions against nano-apatite collagen composites. (2012)
  • Author(s): Hatakeyama, W., Taira, M., Y., Kihara, H., Sasaki, M., Kimura, S., Kondo, H.
  • Journal Title: Nano Biomedicine Volume: 4 Pages: 118-124
  • NAID: 130004679846
  • Peer Reviewed
• [Journal Article] Quantatative real -time RT -PCR analyses of DNA-damage-recovery-related gene expressions of mouse macrophage-like cell line RAW264 when exposed to IC50 nickel ions. (2012)
  • Author(s): Taira, M., Y., Kagiya, T., Sasaki, M., Kimura, S.
  • Journal Title: Nano Biomedicine Volume: 3 Pages: 294-299
  • Peer Reviewed
• [Journal Article] Quantatative real-time RT-PCR analyses of DNA-damage-recovery-related gene expressions of mouse macrophage-like cell line RAW264 when exposed to IC50 nickel ions. (2012)
  • Author(s): Taira, M.
  • Journal Title: Nano Biomedicine Volume: 3 Pages: 294-299
  • Peer Reviewed
• [Journal Article] Proteome analyses of human macrophages exposed to low cytotoxic IC90 copper (2+) ions (2011)
  • Author(s): Taira, M., Shimoyama, Y ., Kagiya, T., Sasaki, M., Nezu, T., Harada, H. and Kimura, S.
  • Journal Title: Dent. Mater. J. Volume: 30 Pages: 293-299
  • NAID: 10029136627
  • Peer Reviewed
• [Journal Article] Quantitative real-time RT-PCR analyses of DNA-damage-recovery-related gene expressions of mouse macrophage-like cell line RAW264 when exposed to IC 50 nickel ions. (2011)
  • Author(s): Taira, M., Kagiya, T., Sasaki, M. and Kimura, S
  • Journal Title: Nano Biomed Volume: 3 Pages: 294-299
  • NAID: 130004555811
  • Peer Reviewed
• [Journal Article] Quantitative real-time RT-PCR analyses of DNA-damage-recovery-related gene expressions of mouse macrophage-like cell line RAW264 when exposed to IC_<50> nickel ions (2011)
  • Author(s): Taira, M.
  • Journal Title: Nano Biomedicine Volume: 3 Pages: 294-299
  • Peer Reviewed
• [Journal Article] Proteome analyses of human macrophages exposed to low cytotoxic IC90 copper (2+) ions (2011)
  • Author(s): Taira, M.
  • Journal Title: Dent.Mater.J. Volume: 30 Pages: 293-299
  • Peer Reviewed
• [Journal Article] Microscopic observations and inflammatory cytokine productions of human macrophage phagocytising submicron titanium particles (2010)
  • Author(s): Taira, M., Kagiya, T., Harada, H., Sasaki, M., Kimura, S., Narushima, T., Nezu, T. and Araki, Y.
  • Journal Title: J. Mater. Sci. Mater. Med. Volume: 21 Pages: 267-275
  • Peer Reviewed
• [Journal Article] Relationship between oral status and prevalence of periodontopathic bacteria on the tongues of elderly individuals (2010)
  • Author(s): Kishi, M., Ohara -Nemoto, Y., Takahashi, M., Kishi, K., Kimura, S. and Yonemitsu, M
  • Journal Title: J. Med. Microbiol. Volume: 59 Pages: 1354-1359
  • NAID: 120006984948
  • Peer Reviewed
• [Journal Article] Amino acid residues modulating the activities of staphylococcal glutamyl endopeptidases (2010)
  • Author(s): Ono, T., Ohara-Nemoto, Y., Shimoyama, Y., Okawara, H., Kobayakawa, T., Baba, T. T., Kimura, S. and Nemoto, T. K.:
  • Journal Title: Biol. Chem Volume: 391 Pages: 1221-1232
  • NAID: 120006984895
  • Peer Reviewed
• [Journal Article] Histological and TEMobservation of subcutaneous tissues exposed to particulate copper,nickel and titanium (2010)
  • Author(s): Saitoh, S., Sasaki, K., Nezu, T., Taira, M., Shimoyama, Y. , Sasaki, M., Kimura, S.and Ishizeki, K
  • Journal Title: J. Oral Tissue Engin Volume: 8 Pages: 102-106
  • NAID: 130004941170
  • Peer Reviewed
• [Journal Article] Microscopic observations and inflammatory cytokine productions of human macrophage phagocytising submicron titanium particles. (2010)
  • Author(s): Taira, M., Kagiya, T., Harada, H., Sasaki, M., Kimura, S., Narushima, T., Nezu, T., Araki, Y.
  • Journal Title: J.Mater.Sci.Mater.Med. Volume: 21 Pages: 267-275
  • Peer Reviewed
• [Journal Article] Histological and TEM observation of subcutaneous tissues exposed to particulate copper, nickel and titanium. (2010)
  • Author(s): Saitoh, S., Sasaki, K., Nezu, T., Taira, M., Shimoyama, Y., Sasaki, M., Kimura, S., Ishizeki, K.
  • Journal Title: J.Oral Tissue Engin. Volume: 8 Pages: 102-106
  • NAID: 130004941170
  • Peer Reviewed
• [Presentation] The aciduricity inStreptococcus anginosus (2013)
  • Author(s): Sasaki, M., Kodama, Y., Shimoyama, Y ., Kimura, S.:
  • Organizer: 91th Genera l Session & Exhibition of the International Association of Dental Research (IADR)
  • Place of Presentation: Siattle, USA
  • Year and Date: 2013-03-21
• [Presentation] Nested PCRを用いた小児口腔へのPorphyromonas gingivalis 線毛タイプ別感染実態の検討. (2013)
  • Author(s): 下山 佑,木村美澄,佐々木実,根本優子,古玉芳豊,上戸幸美,田中光郎,木村重信
  • Organizer: 第86回日本細菌学会総会
  • Place of Presentation: 幕張
  • Year and Date: 2013-03-20
• [Presentation] The aciduricity in Streptococcus anginosus. (2013)
  • Author(s): Sasaki, M.
  • Organizer: 91th General Session & Exhibition of the International Association of Dental Research
  • Place of Presentation: Seattle, USA
• [Presentation] Nested PCRを用いた小児口腔へのPorphyromonas gingivalis 線毛タイプ別感染実態の検討 (2013)
  • Author(s): 下山 佑
  • Organizer: 第86回日本細菌学会総会
  • Place of Presentation: 幕張，千葉
• [Presentation] Streptococcus anginosusの耐酸性に関わる酵素の役割 (2012)
  • Author(s): 佐々木実,古玉芳豊,下山 佑,木村重信
  • Organizer: 第54回歯科基礎医学会学術大会
  • Place of Presentation: 郡山
  • Year and Date: 2012-09-16
• [Presentation] A Novel Fibronectin Binding Protein of Streptococcus intermedius. (2012)
  • Author(s): Sasaki, M., Kodama, Y., Shimoyama, Y., Kimura, S
  • Organizer: 90th General Session & Exhibition of the International Association of Dental Research (IADR)
  • Place of Presentation: Iguacu Falls, Brazil
  • Year and Date: 2012-06-21
• [Presentation] Streptococcus intermediusのフィブロネクチン結合タンパク質による上皮細胞付着機序 (2012)
  • Author(s): 古玉芳豊,佐々木 実,下山 佑,上戸幸美,木村重信
  • Organizer: 第85回日本細菌学会総会
  • Place of Presentation: 長崎
  • Year and Date: 2012-03-27
• [Presentation] Streptococcus anginosusの耐酸性に関わる酵素の役割 (2012)
  • Author(s): 佐々木実
  • Organizer: 第54回歯科基礎医学会学術大会
  • Place of Presentation: 郡山，福島
• [Presentation] A Novel Fibronectin Binding Protein of Streptococcus intermedius. (2012)
  • Author(s): Sasaki, M
  • Organizer: 90th General Session & Exhibition of the International Association of Dental Research
  • Place of Presentation: Iguas Falls, Brzil
• [Presentation] Streptococcus anginosusのフィブロネクチン結合タンパク質のマウスにおける病原性の解析 (2011)
  • Author(s): 佐々木 実,古玉芳豊,下山 佑,木村重信
  • Organizer: 第53回歯科基礎医学会学術大会
  • Place of Presentation: 岐阜
  • Year and Date: 2011-10-01
• [Presentation] The pathogenic involvement of the fibronectin binding protein, Fbp62, in Streptococcus anginosus infection. (2011)
  • Author(s): Sasaki, M., Kodama, Y., Shimoyama, Y ., Agato, S. and Kimura, S.
  • Organizer: International Union of Microbiological Societies 2011 Congress (IUMS 2011)
  • Place of Presentation: Sapporo, Japan
  • Year and Date: 2011-09-07
• [Presentation] The pathogenic involvement of the fibronectin binding protein, Fbp62, in Streptococcus anginosus infection (2011)
  • Author(s): Sasaki, M.
  • Organizer: International Union of Microbiological Societies 2011 Congress
  • Place of Presentation: Sapporo
  • Year and Date: 2011-09-07
• [Presentation] Fbp62, fibronectin binding protein of Streptococcus anginosus involves the virulence in mouse infection (2011)
  • Author(s): Sasaki, M.
  • Organizer: 10th World Congress on Inflammation 2011
  • Place of Presentation: Paris
  • Year and Date: 2011-06-27
• [Presentation] Fbp62, fibronectin binding protein of Streptococcus anginosus involves the virulence in mouse infection. (2011)
  • Author(s): Sasaki, M., Kodama, Y., Shimoyama, Y., Ishikawa, T. and Kimura, S.
  • Organizer: 10th World Congress on Inflammation 2011
  • Place of Presentation: Paris, France
  • Year and Date: 2011-06-26
• [Presentation] Auto-catalytic propeptide processing facilitates the final hetero-catalytic maturation of glutamyl endopeptidase GluV8. (2011)
  • Author(s): Ohara -Nemoto, Y., Rouf, S.M.A., Shimoyama, Y., Kimura, S. , Ono, T. and Nemoto, T.K.
  • Organizer: 111th General Meeting of the American Society for Microbiology.
  • Place of Presentation: New Orleans, USA
  • Year and Date: 2011-05-24
• [Presentation] Fibronectin binding activity of Streptococcus anginosus promotes the adherence to mucosal epithelial cells. (2011)
  • Author(s): Sasaki, M., Kodama, Y., Shimoyama, Y., Ishikawa, T. and Kimura, S.
  • Organizer: 4th International Symposium for Interface Oral Health Science in Sendai
  • Place of Presentation: Sendai, Japan
  • Year and Date: 2011-03-08
• [Presentation] Rapid identification of Abiotrophia/Granulicatella species using by 16S rRNA based PCR and RFLP. (2011)
  • Author(s): Shimoyama, Y., Sasaki, M., Ohara-Nemoto, Y., Nemoto, T. K., Ishikawa, T. and Kimura, S
  • Organizer: 4th International Symposium for Interface Oral Health Science in Sendai
  • Place of Presentation: Sendai, Japan
  • Year and Date: 2011-03-08
• [Presentation] Maternal transmission of mutans and other oral streptococcal species (2011)
  • Author(s): Otake -Asakawa, A., Harada-Oikawa, R., Ohara-Nemoto, Y., Tanaka, M. and Kimura, S.
  • Organizer: 4th International Symposium for Interface Oral Health Science in Sendai
  • Place of Presentation: Sendai, Japan
  • Year and Date: 2011-03-08
• [Presentation] In vitro adherence of Candida albicans to acrylic resin with different surface status (2011)
  • Author(s): Nomura, T., Suzuki, T., Furuya, J., Shimoyama, Y., Sasaki, M. and Kimura, S.
  • Organizer: 4th International Symposium for Interface Oral Health Science in Sendai.
  • Place of Presentation: Sendai, Japan
  • Year and Date: 2011-03-08
• [Presentation] Macrophage reaction against sub-micron titanium particles (2011)
  • Author(s): Taira, M., Sasaki, M. and Kimura, S.
  • Organizer: 4th International Symposium for Interface Oral Health Science in Sendai.
  • Place of Presentation: Sendai, Japan
  • Year and Date: 2011-03-08
• [Presentation] Fibronectin binding activity of Streptococcus anginosus promotes the adherence to mucosal epithelial cells. (2011)
  • Author(s): Sasaki, M., Kodama, Y., Shimoyama, Y., Ishikawa, T., Kimura, S.
  • Organizer: 4th International Symposium for Interface Oral Health Science
  • Place of Presentation: Sendai
  • Year and Date: 2011-03-08
• [Presentation] Rapid identification of Abiotrophia/Granulicatella species using by 16S rRNA based PCR and RFLP. (2011)
  • Author(s): Shimoyama, Y., Sasaki, M., Ohara-Nemoto, Y., Nemoto, T.K., Ishikawa, T., Kimura, S.
  • Organizer: 4th International Symposium for Interface Oral Health Science
  • Place of Presentation: Sendai
  • Year and Date: 2011-03-08
• [Presentation] In vitro adherence of Candida albicans to acrylic resin with different surface status. (2011)
  • Author(s): Nomura, T., Suzuki, T., Furuya, J., Shimoyama, Y., Sasaki, M., Kimura, S.
  • Organizer: 4th International Symposium for Interface Oral Health Science
  • Place of Presentation: Sendai
  • Year and Date: 2011-03-08
• [Presentation] Macrophage reaction against sub-micron titanium particles. (2011)
  • Author(s): Taira, M., Sasaki, M., Kimura, S.
  • Organizer: 4th International Symposium for Interface Oral Health Science
  • Place of Presentation: Sendai
  • Year and Date: 2011-03-08
• [Presentation] Nutritionally variant streptococciの新規迅速同定法の開発 (2010)
  • Author(s): 下山 佑,佐々木 実,石河太知,古玉芳豊,木 村 重 信
  • Organizer: 第36回岩手医科大学歯学会総会
  • Place of Presentation: 盛岡
  • Year and Date: 2010-12-04
• [Presentation] ストレプトアビジン付き磁性マイクロビーズを用いた単球の磁気回収に関する研究 (2010)
  • Author(s): 平 雅之,佐々木 実, 木村重信
  • Organizer: 第52回歯科基礎医学会学術大会総会
  • Place of Presentation: 東京
  • Year and Date: 2010-09-22
• [Presentation] Anginosus group streptococciのフィブロネクチン結合タンパク質の解析 (2010)
  • Author(s): 古玉芳豊,佐々木 実,下山 佑,石河太知,木村重信
  • Organizer: 第52回歯科基礎医学会学術大会総会
  • Place of Presentation: 東京
  • Year and Date: 2010-09-22
• [Presentation] Nutritionally variant streptococciの新規迅速同定法の開発 (2010)
  • Author(s): 下山 佑,佐々木 実,石河太知,根本優子,根 本 孝 幸 ,木 村 重 信
  • Organizer: 第52回歯科基礎医学会学術大会・総会
  • Place of Presentation: 東京
  • Year and Date: 2010-09-22
• [Presentation] ストレプトアビジン付き磁性マイクロビーズを用いた単球の磁気回収に関する研究 (2010)
  • Author(s): 平雅之, 佐々木実, 木村重信
  • Organizer: 第52回歯科基礎医学会学術大会・総会
  • Place of Presentation: 東京
  • Year and Date: 2010-09-22
• [Presentation] Anginosus group streptococciのフィブロネクチン結合タンパク質の解析 (2010)
  • Author(s): 古玉芳豊, 佐々木実, 下山佑, 石河太知, 木村重信
  • Organizer: 第52回歯科基礎医学会学術大会・総会
  • Place of Presentation: 東京
  • Year and Date: 2010-09-22
• [Presentation] Nutritionally variant streptococci の新規迅速同定法 (2010)
  • Author(s): 下山 佑,佐々木 実,石河太知,木村重信
  • Organizer: 第64回日本細菌学会 東北支部総会
  • Place of Presentation: 仙台
  • Year and Date: 2010-08-19
• [Presentation] Nutritionally variant streptococciの新規迅速同定法 (2010)
  • Author(s): 下山佑, 佐々木実, 石河太知, 木村重信
  • Organizer: 第64回日本細菌学会 東北支部総会
  • Place of Presentation: 仙台
  • Year and Date: 2010-08-19
• [Presentation] Structural chemistry of Staphylo coccus aureus glutamyl endopeptidase. (2010)
  • Author(s): Ohara -Nemoto, Y., Rouf, S.M.A., Shimoyama, Y., Kimura, S. and Nemoto, T.K.
  • Organizer: 88th General Session & Exhibition of the IADR
  • Place of Presentation: Barcelona, Spain
  • Year and Date: 2010-07-16
• [Presentation] SLPI production from gingival epithelial cells against Porphyromonas gingivalis infection. (2010)
  • Author(s): Ishikawa, T., Ohara-Nemoto, Y., Shimoyama, Y., Sasaki, M., Kimura, S.
  • Organizer: 88th General Session & Exhibition of the IADR
  • Place of Presentation: Barcelona (Spain)
  • Year and Date: 2010-07-16
• [Presentation] SLPI production from gingival epithelial cells against Porphyromonas gingivalis infection. (2010)
  • Author(s): Ishikawa, T., Ohara-Nemoto, Y., Shimoyama, Y., Sasaki, M. and Kimura, S
  • Organizer: 88th General Session & Exhibition of the IADR.
  • Place of Presentation: Barcelona, Spain
  • Year and Date: 2010-07-15
• [Presentation] Maternal transmission of mutans and other oral streptococcal species. (2010)
  • Author(s): Otake -Asakawa, A., Kimura, S. , Asakawa, T. and Tanaka, M.
  • Organizer: 88th General Session & Exhibition of the IADR.
  • Place of Presentation: Barcelona, Spain
  • Year and Date: 2010-07-15
• [Presentation] Adhesion mechanism of Streptococcus anginosus to mucosal epithelial cells. (2010)
  • Author(s): Kodama, Y., Sasaki, M., Shimoyama, Y., Tajika, S. and Kimura, S.
  • Organizer: 20th European Congress of Clinical Microbiology and Infectious Diseases (20th ECCMID 2010)
  • Place of Presentation: Vienna, Austria
  • Year and Date: 2010-04-13
• [Presentation] Adhesion mechanism of Streptococcus anginosus to mucosal epithelial cells. (2010)
  • Author(s): Kodama, Y., Sasaki, M., Shimoyama, Y., Tajika, S., Kimura, S.
  • Organizer: 20th European Congress of Clinical Microbiology and Infectious Diseases
  • Place of Presentation: Vienna (Austria)
  • Year and Date: 2010-04-13
• [Book] Pathogenesis and Treatment of Periodontitis (2012)
  • Author(s): Kimura, S., Ohara-Nemoto, Y., Shimoyama, Y., Ishikawa, T., and Sasaki, M.
  • Publisher: In Periodontitis, InTech:Pathogenic factors of Porphyromonas gingivalis and the host difence mechanisms.
• [Book] Fibronectin binding activity of Streptococcus anginosus promotes the adherence to mucosa l epithelial cells. In Interface Oral Health Science 2011 (2012)
  • Author(s): Sasaki, M., Kodama, Y., Shimoyama, Y. , Ishikawa, T. and Kimura, S
  • Publisher: Springer Japan, Tokyo
• [Book] Rapid identification of Abiotrophia/Gr anulicatella species using by 16S rRNA based PCR and RFLP In Interface Oral Health Science 2011 (2012)
  • Author(s): Shimoyama, Y., Sasaki, M. , Ohara -Nemoto, Y., Nemoto, T. K., Ishikawa, T. and Kimura, S.
  • Publisher: Springer Japan, Tokyo
• [Book] Mate rnal transmission of mutans and other oral streptococcal species. In Interface Oral Health Science 2011 (2012)
  • Author(s): Otake-Asakawa, A., Harada-Oikawa, R., Ohara-Nemoto, Y., Tanaka, M. and Kimura, S.
  • Publisher: Springer Japan, Tokyo
• [Book] In vitro adherence of Candida albicans to acrylic resin with different surface status. In Interface Oral Health Science 2011 (2012)
  • Author(s): Nomura, T., Suzuki, T., Furuya, J., Shimoyama, Y. , Sasaki, M. and Kimura, S.
  • Publisher: Springer Japan, Tokyo
• [Book] Macrophage reaction against sub-micron titanium particles.In Interface Oral Health Science 2011 (2012)
  • Author(s): Taira, M., Sasaki, M. and Kimura, S.
  • Publisher: Springer Japan, Tokyo
• [Book] Pathogenesis and Treatment of Periodontitis (2012)
  • Author(s): Kimura, S.
  • Total Pages: 200
  • Publisher: InTech
• [Book] Interface Oral Health Science 2011 (2012)
  • Author(s): Sasaki, M.
  • Publisher: Springer(in press)
• [Book] Interface Oral Health Science 2011 (2012)
  • Author(s): Shimoyama, Y.
  • Publisher: Springer(in press)
• [Book] Interface Oral Health Science 2011 (2012)
  • Author(s): Taira, M.
  • Publisher: Springer(in press)
• [Book] Interface Oral Health Science 2011 (2012)
  • Author(s): Nomura, T.
  • Publisher: Springer(in press)
• [Remarks]
  • URL: http://hitech-d.iwate-med.ac.jp/micr/index.htm