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Biological investigation of antimicrobial peptides for the regulation of fungal infections

Research Project

Project/Area Number 14370604
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field 病態科学系歯学(含放射線系歯学)
Research InstitutionKochi Medical School

Principal Investigator

UETA Eisaku  Kochi Medical School, Department of Oral Surgery, Assistant Professor, 医学部附属病院, 講師 (10203431)

Co-Investigator(Kenkyū-buntansha) OKU Naohisa  Kochi Medical School, Department of Oral Surgery, Research Associate, 医学部附属病院, 助手 (20363286)
KAMATANI Takaaki  Kochi Medical School, Department of Oral Surgery, Research Associate, 医学部附属病院, 助手 (00315003)
SASABE Eri  Kochi Medical School, Department of Oral Surgery, Research Associate, 医学部附属病院, 助手 (40363288)
OSAKI Toki  Kochi Medical School, Department of Oral Surgery, Professor, 医学部, 教授 (70031995)
木村 剛  高知医科大学, 医学部附属病院, 助手 (10294836)
山本 哲也  高知医科大学, 医学部, 助教授 (00200824)
Project Period (FY) 2002 – 2003
Project Status Completed (Fiscal Year 2003)
Budget Amount *help
¥9,700,000 (Direct Cost: ¥9,700,000)
Fiscal Year 2003: ¥4,400,000 (Direct Cost: ¥4,400,000)
Fiscal Year 2002: ¥5,300,000 (Direct Cost: ¥5,300,000)
Keywordsantimicrobial peptide / α-defensin / β-defensin / Peptide 2 / cytochrome P450 / candidiasis / aspergillosis / neutrophils / Peptide2 / チトクロームp450 / カンジタ症
Research Abstract

We examined the antifungal mechanisms of antimicrobial peptides including lactoferrin peptide, Peptide 2, which was made by our laboratoies.
1. Peptide 2 possesses stronger antifungal effect against both C.albicans and A.fumigatus than α-defensin-1 and β-defesin-2.
2. Peptide 2 and Histatin 5 show additive and synergistic effects with amphotericin B and intraconazol, respectively.
3. Intracellular concentration of the antifungal drugs increased when the fungi were treated with a combination with each antifungal drug and Peptide 2, Histatin 5 or α-defensin-1.
4. Each antimicrobial peptide weakly inhibited syntheses of Candida cell wall (chicin, mannan, glucan) and DNA but did not inhibit the cytochrome P450 activity of each fungus. Each antimicrobial peptide increased ATP-efflux from Candida cells with no increase of the membrane permeability.
5. Each antimicrobial peptide, especially Peptide 2, prolonged the survival periods of Candida- and Aspergillus-infected mice cooperating with each antifungal drug.
6.Although both antifungal drugs increased the multidrug-resistance gene (MDR1), Peptide 2 and Histatin 5 did not increase the MDR1 and bothe peptides revealed almost equal anticellular activities against amphotericin B-resistant Candida cells.
7. In the peptide examined, only Peptide 2 enhanced neutrophil killing activity and reactive oxygen species (ROS)-generating activity.
8. Peptide 2, but not other peptides, increased ROS generation and phagocytosis of neutrophils activating the signal pathway of G protein, PI3K, PKC, PAK1 and ERK1/2 and increasing the expression of Rac2/Cdc2,p47^<phox> and p67^<phox>.
These results suggest that Peptide 2 is clinically useful for treatment of fungal infections.

Report

(3 results)
  • 2003 Annual Research Report   Final Research Report Summary
  • 2002 Annual Research Report
  • Research Products

    (10 results)

All 2004 2003 Other

All Journal Article (8 results) Publications (2 results)

  • [Journal Article] Regulation of fungal infection by combination of amphotericin B and Peptide 2, a lactoferrin peptide that activates neutrophils2004

    • Author(s)
      Tetsuro Okamoto
    • Journal Title

      Clinical and Diagnostic Laboratory Immunology 11・6

      Pages: 1111-1119

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Journal Article] Regulation of fungal infection by a combination of amphotericin B and Peptide 2, a lactoferrin peptide that activates neutrophils2004

    • Author(s)
      Tetsuro Okamoto
    • Journal Title

      Clinical and Diagnostic Laboratory Immunology 11(6)

      Pages: 1111-1119

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Journal Article] Decreased excretion of antimicrobial proteins and peptides in saliva of patients with oral candidiasis2003

    • Author(s)
      Toyohiro Tanide
    • Journal Title

      Journal of Oral Pathology & Medicine 32・10

      Pages: 586-594

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Journal Article] 唾液分泌低下-その原因と唾液分泌低下に伴う口腔障害2003

    • Author(s)
      植田栄作
    • Journal Title

      日本口腔科学会雑誌 52.5

      Pages: 277-234

    • NAID

      10014354043

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Journal Article] 不死化唾液腺細胞における抗菌性ペプタイドの発現と産生2003

    • Author(s)
      山本哲也
    • Journal Title

      日本口腔組織培養学会誌 12・1

      Pages: 63-64

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Journal Article] Decreased excretion of antimicrobial proteins and peptides in saliva of patients with oral candidiasis2003

    • Author(s)
      Toyohiro Tanida
    • Journal Title

      Journal of Oral Pathology & Medicine 32(10)

      Pages: 586-594

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Journal Article] The cause of hyposalivation and hyposalivation-induced oral impairment2003

    • Author(s)
      Eisaku Ueta
    • Journal Title

      Journal of the Japanese Stomatological Society 52(5)

      Pages: 227-234

    • NAID

      10014354043

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Journal Article] Expression and generation of antimicrobial peptides in the immortalized human salivary gland cells2003

    • Author(s)
      Tetsuya Yamamoto
    • Journal Title

      The Japanese Journal of Tissue Culture Society for Dental Research 12(1)

      Pages: 63-64

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Toyohiro Tanida: "Decreased excretion of antimicrobial proteins and peptides in saliva of patients with oral candidiasis."Journal of Oral Pathology & Medicine. 32・10. 586-594 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] 植田 栄作: "唾液分泌低下-その原因と唾液分泌低下に伴う口腔障害"日本口腔科学会雑誌. 52・5. 227-234 (2003)

    • Related Report
      2003 Annual Research Report

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Published: 2002-04-01   Modified: 2016-04-21  

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