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Development of bovine milk antibody to prevent dental caries

Research Project

Project/Area Number 12357013
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section展開研究
Research Field 矯正・小児・社会系歯学
Research InstitutionKyushu University

Principal Investigator

SHIMAZAKI Yoshihiro (2001-2003)  Kyushu University, Faculty of Dental Science, Assistant, 大学院・歯学研究院, 助手 (10291519)

古賀 敏比古 (2000)  九州大学, 歯学研究院, 教授 (10037541)

Co-Investigator(Kenkyū-buntansha) NAKANO Yutaka  Kyushu University, University Farm, Faculty of Agriculture, Assistant, 農学部附属農場, 助手 (20243925)
OKANO Kaoru  Kyushu University, University Farm, Faculty of Agriculture, Assoc.Prof., 農学部附属農場, 助教授 (40038328)
OHO Takahiko  Kyushu University, University Hospital, Assistant Prof., 講師 (50160940)
嶋崎 義浩  九州大学, 歯学研究院, 助手 (10291519)
Project Period (FY) 2000 – 2003
Project Status Completed (Fiscal Year 2003)
Budget Amount *help
¥40,900,000 (Direct Cost: ¥34,600,000、Indirect Cost: ¥6,300,000)
Fiscal Year 2003: ¥9,100,000 (Direct Cost: ¥7,000,000、Indirect Cost: ¥2,100,000)
Fiscal Year 2002: ¥8,580,000 (Direct Cost: ¥6,600,000、Indirect Cost: ¥1,980,000)
Fiscal Year 2001: ¥9,620,000 (Direct Cost: ¥7,400,000、Indirect Cost: ¥2,220,000)
Fiscal Year 2000: ¥13,600,000 (Direct Cost: ¥13,600,000)
KeywordsDental caries / Milk / Cariogenic bacteria / Colonization Factor / う触 / う触細菌 / ラ蝕 / ラ細菌
Research Abstract

Cell surface Protein antigen(PAc) and water-insoluble glucan-synthesizing enzyme(GTF-I) produced by cariogenic Streptococcus mutans are two major factors implicated in the colonization of the human oral cavity by this bacterium. We examined the effect of bovine milk, produced after immunization with a fusion protein of functional domains of these proteins, on the recolonizaion of S.mutans. To prerare immune milk, a pregnant Holstein cow was immunized with the fusion protein PAcA-GB, a fusion of the saliva-binding alanine-rich region(PAcA) of PAc and the glucan-binding(GB) domain of GTF-I. After eight adult subjects received cetylpyridinium chloride(CPC) treatment, one subgroup(n=4) rinsed their mouths with immune milk arid a control group(n=4) rinsed with nonimmune milk. S.mutans levels in saliva and dental plaque decreased after CPC treatment in both groups. Mouth rinsing with immune milk significantly inhibited recolonization of S.mutans in saliva and plaque. On the other hand, the n … More umber of S.mutans cells in saliva and plaque in the control group increased immediately after the CPC treatment and surpassed the baseline level 42 and 28 days, respectively, after the CPC treatment. The ratios of S.mutans to total streptococci in saliva and plaque in the group that received immune milk were lower than those in the control group. These results suggest that milk produced from immunized cow may be useful for controlling S.mutans in the human oral cavity.
We examined the effect of the immune milk on the cariogenicity of S.mutans in a rat model. Concentrated immune milk was fed to rats once a day for 55 days. The group that received immune milk had significantly less caries development than controls.
The bovine lactoferrin molecule and relatively long lactoferrin fragments containing residues 473 to 538 strongly inhibited adherence of S.mutans to saliva-coated hydroxyapatite beads. Each cysteine residue in Lf411(residents 473 to 538) was replaced by a serine residue, and the mutants Lf411-C481S and Lf411-C532S strongly inhibited S.mutans adherence. These results suggests that the functional domain of lactoferrin that binds to a salivary film lies in residues 473 to 538 and that region might be concealed by disulfide bond formation between Cys481 and Cys532 in the Lf411 fragment. Less

Report

(5 results)
  • 2003 Annual Research Report   Final Research Report Summary
  • 2002 Annual Research Report
  • 2001 Annual Research Report
  • 2000 Annual Research Report
  • Research Products

    (32 results)

All Other

All Publications (32 results)

  • [Publications] Morihide Mitoma, et al.: "Inhibitory effect of bovine milk lactoferrin on the interaction between α Streptococcal surface protein antigen and human salivary agglutinin"The Journal of Biological Chemistry. Vol.276 No.21. 18060-18065 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Hiroko Kawagoe, et al.: "Production of goat milk antibodies against cell surface protein antigen-glucosyltransferase fusion protein of Streptococcus mutans"J.Fac.Agr., Kyushu Univ.. Vol.507. 495-507 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Yoshihiro Shimazaki, et al.: "Passive immunization with milk produced from an immunized cow prevents oral recolonization by Streptococcus mutans"Clinical and Diagnostic Laboratory Immunology. Vol.8 No.6. 1136-1139 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Morihide Mitoma, et al.: "Passive immunization with bovine milk containing antibodies to a cell surface protein antigen-glucosyltransferase fusion protein protects rats against dental caries"Infection and Immunity. Vol.70 No.5. 2721-2724 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Toshihiko Koga, et al.: "Immunization against dental caries"Vaccine. Vol.20. 2027-2044 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Yukie Shibata, et al.: "Expression and characterization of streptococcal rgp genes required for rhamnan synthesis in Escherichia coli"Infection and Immunity. Vol.70 No.9. 2891-2898 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Takahiko Oho, et al.: "Functional domain of bovine milk lactoferrin which inhibits the adherence of Streptococcus mutans cells to a salivary film"Infection and Immunity. Vol.70 No.9. 5279-5282 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kazuhisa Ozaki, et al.: "A novel mechanism for glucose side-chain formation in rhamnose-glucose polysaccharide synthesis"FEBS Letters. Vol.532. 159-163 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Hiromasa Tsuda, et al.: "Genes involved in bacitracin resistance in Streptococcus mutans"Antimicrobial Agents and Chemotherapy. Vol.46 No.12. 3756-3764 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] 古賀俊比古: "齲蝕予防のフロンティア「歯科医学と健康の創造 歯界展望(増刊号)」"医師薬出版. 176-179 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Mitoma M., Oho T., Shimazaki Y., Koga T.: "Inhibitory effect of bovine milk lactoferrin on the interaction between a streptococcal surface protein antigen and human salivary agglutinin."J.Biol.Chem.. 276. 18060-18065 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kawagoe H., Oho T., Okano K., Nakano Y., Ono Y., Shimazaki Y., Yamashita Y., Koga T., Fukuyama M., Fujihara N.: "Production of goat milk antibodies against cell surface protein antigen-glucosyltransferase fusion protein of Streptococcus mutans."J.Fac.Agr., Kyushu Univ.. 495-507 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Shimazaki Y., Mitoma M., Oho T., Nakano Y., Yamashita Y., Okano K., Nakano Y., Fukuyama M., Fujihara N., Nada Y., Koga T.: "Passive immunization with milk produced from an immunized cow prevents oral recolonization by Streptococcus mutans."Clin.Diagn.Lab.Immunol.. 8. 1136-1139 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Mitoma M., Oho T., Michibata N., Okano K., Nakano Y., Fukuyama M., Koga T.: "Passive immunization with bovine milk containing antibodies to a cellsurface protein antigen-glucosyltransferase fusion protein protects rats against dental caries."Infect.Immun.. 70. 2721-2724 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Koga T., Oho T., Shimazaki Y., Nakano Y.: "Immunization against dental caries."Vaccine. 20. 2027-2044 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Shibata Y., Yamashita Y., Ozaki K., Nakano Y., Koga T.: "Expression and characterization of streptococcal rgp genes required for rhamnan synthesis in Escherichia coli."Infect.Immun.. 70. 2891-2898 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Oho T., Mitoma M., Koga T.: "Functional domain of bovine milk lactoferrin which inhibits the adherence of Streptococcus mutans cells to a salivary film."Infect.Immun.. 70. 5279-5282 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Ozaki K., Shibata Y., Yamashita Y., Nakano Y., Tsuda H., Koga T.: "A novel mechanism for glucose side-chain formation in rhamnose-glucose polysaccharide synthesis."FEBS Lett. 532. 159-163 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Tsuda H., Yamashita Y., Shibata Y., Nakano Y., Koga T.: "Genes involved in bacitracin resistance in Streptococcus mutans."Antimicrob.Agents Chemother.. 46. 3756-3764 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Koga T.: "Frontier of preventive of dental caries. Creation of dental medicine and health."Dental Outlook. (Suppl.). 176-179 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Toshihiko Koga, et al.: "Immunization against dental caries"Vaccine. Vol. 20. 2027-2044 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Morihide Mitoma, et al.: "Passive immunization with bovine milk containing antibodies to a cell surface protein antigen-glucosyltransferase fusion protein protects rats against dental caries"Infection and Immunity. Vol. 70 No. 5. 2721-2724 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Yukie Shibata, et al.: "Expression and characterization of streptococcal rgp genes required for rhamnan synthesis in Escherichia coli"Infection and Immunity. Vol. 70 No. 6. 2891-2898 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Takahiko Oho, et al.: "Functional domain of bovine milk lactoferrin which inhibits the adherence of Streptococcus mutans cells to a salivary film"Infection and Immunity. Vol. 70 No. 9. 5279-5282 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Kazuhisa Ozaki, et al.: "A novel mechanism for glucose side-chain formation in rhamnose-glucose polysaccharide synthesis"FEBS Letters. Vol. 532. 159-163 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Hiromasa Tsuda, et al.: "Genes involved in bacitracin resistance in streptococcus mutans"Antimicrobial Agents and Chemotherapy. Vol. 46 No. 12. 3756-3764 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Morihide Mitoma, et al.: "Inhibitory effect of bovine milk lactoferrin on the interaction between a Streptococcal surface protein antigen and human salivary agglutinin"The Journal of Biological Chemistry. Vol.276 No.21. 18060-18065 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Yoshihiro Shimazaki, et al.: "Passive immunization with milk produced from an immunized cow prevents oral recolonization by Streptococcus mutans"Clinical and Diagnostic Laboratory Immunology. Vol.8 No.6. 1136-1139 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Tsuda,T. 他7名: "The role of serotype-specific polysaccharide in the resistance of S.mutans to phagocytosis by human polymorphonuclear leukocytes"Infect.Immun.. 68. 644-650 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Oho,T. 他4名: "Simple and rapid detection of Streptococcus mutans and Streptococcus sobrinus in human saliva by PCR"Oral Microbiol.Immunol.. 15. 258-262 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] 古賀敏比古: "齲蝕予防のフロンティア"歯界展望. 増刊. 176-179 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Yamashita,Y. 他4名: "Streptococci and Streptococcal Diseases : Entering the new Millennium"D.R.Martin, and J.R.Tagg (Securacopy). 926 (2000)

    • Related Report
      2000 Annual Research Report

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Published: 2000-04-01   Modified: 2016-04-21  

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