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Basic Study on the protection of virus infection coinfected with MRSA.

Research Project

Project/Area Number 13670141
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Pathological medical chemistry
Research InstitutionKobe University

Principal Investigator

HIJIKATA Akiko  Kobe University, School of Medicine, Associate Professor, 医学部, 助教授 (10107948)

Co-Investigator(Kenkyū-buntansha) KONISHI Eiji  Kobe University, School of Medicine, Associate Professor, 医学部, 助教授 (40135786)
KATAOKA Nobumasa  Kobe University, School of Medicine, Associate Professor, 医学部, 助教授 (80071398)
Project Period (FY) 2001 – 2002
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2002: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2001: ¥2,400,000 (Direct Cost: ¥2,400,000)
Keywordsprotease / virus / plasmin / inhibitor / infection / カリクレイン
Research Abstract

This study was undertaken to clarify the possible role of proteases of Staphylococcus aureus and the coagulation/fibrinolysis enzymes activated by the S.a aureus proteases in the viral infection, and to evaluate the efficacy of protease inhibitors in the protection of viral infection.
First, we studied the activation of Sendai virus by serine proteases and its inhibition by synthetic inhibitors using LLC-MK_2 cells. Treatment with plasmin and trypsin increased the infective titers of Sendai virus dose-dependently, whereas thrombin and tryptase had no detectable effect on activation within a dose range used in the present study. PASI535 (Nα- (4-aminomethylbenzoyl) -4- (3-picoryloxy)- L-phenylalanine n-hexyl-amide) and MNAPPA ((2R,4R) -4-Phenyl-[Nα- (7-methoxy-2-naphthalene-sulfonyl) -L-arginyl]-2-piperidinecarboxylic acid), active site-directed inhibitors of plasmin and trypsin respectively, inhibited plasmin-induced and trypsin-induced virus activation of Sendai virus. The present study … More provided an experimental basis for potential use of active site-directed synthetic inhibitors as preventive tools for viral infection in vitro.
Second, we studied the protease activity of culture supernatant of S.auzeus obtained from urine of a patient suffering from urinary tract infection. The amidase activity and clotting activity revealed after the addition of ammonium sulfate fraction of the culture supernatant and euglobulin fraction of human plasma together, while these activities of ammonium sulfate fraction or euglobulin traction alone were undetectable or negligible small. The synthetic thrombin inhibitor argatroban ((2R, 4R) -l-[N^2- (3-methyl-l, 2, 3, 4-tetrahydro-8- quinolinesulfonyl) -L-arginyl]-4-methyl-2-piperidinecarboxylic acid) has been clinically used as a therapeutic remedy for the treatment of thrombotic disorders. We found a new effect of argatroban as a potent staphylothrombin inhibitor to inhibit fibrin formation induced by Staphylococcus aureus. Potent staphylothrombin inhibitor would be a useful tool to clarify and evaluate the role of coagulase/staphylothrombin/fibrin in the pathogenesis of S.aureus. Less

Report

(3 results)
  • 2002 Annual Research Report   Final Research Report Summary
  • 2001 Annual Research Report
  • Research Products

    (23 results)

All Other

All Publications (23 results)

  • [Publications] 奥宮明子: "セリンプロテアーゼのセンダイウイルス活性化作用と小分子インヒビターによるその阻害"神戸大学医学部保健学科紀要. 18. 143-148 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Hijikata-Okunomiya A: "Argatroban inhibits staphylothrombin"J Thromb Haemost. 1(in press). (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Osawa K: "Evaluation of antibacterial efficacy of drugs for urinary tract infections by genotyping based on pulsed-field gel electrophoresis (PFGE)"J Infect Chemother. 8. 353-357 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Konishi E: "Dengue type 2 virus subviral extracellular particles produced by a stably transfected mammalian cell line and their evaluation for a subunit vaccine"Vaccine. 20. 1058-1067 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Naoi K: "A new approach for the analysis of seroprevalence data : a mathematical analysis of the seroprevalence of Toxoplasma gondii infection in Hyogo prefecture (Japan) with an implication of periodic outbreaks among young children"Japanese Journal of Tropical Medicine and Hygiene. 30. 99-102 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Konishi E: "Ratios of subclinical to clinical Japanese encephalitis (JE) virus infections in vaccinated populations : evaluation of an inactivated JE vaccine by comparing the ratios with those in unvaccinated populations"Vaccine. 21. 98-107 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Hijikata-Okunomiya A: "Proteolytic activation of Sendai virus and its inhibition by active-site-directed synthetic inhibitors"ShindailHokenkiyou. 18. 143-148 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Hijikata-Okunomiya A: "Argatroban inhibits staphylothrombin"J Thromb Haemost. (in press). (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Tada M: "Structure-activity relationships of plasmin and plasma kallikrein inhibitors. Isolation of plasma kallikrein by high efficiency affinity chromatography and its characterization"Biol Pharm Bull. 24 (5). 520-524 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Tomoo K: "Binding diversity of a noncovalent-type low molecular weight serine protease inhibitor and function of acatalytic water molecule :"J Biochem. 129. 455-460 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Hijikata-Okunomiya A: "Argatroban and its derivatives"Platelets. 12. 184 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Tsuda Y: "Structure-activily relationships of plasmin and plasma kallikrein inhibitors"In Peptide Science 2000 (Ed., Shioiri T). 167-170 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Osawa K: "Evaluation of antibacterial efficacy of drugs for urinary tract infections by genotyping based on pulsed-field gel electrophoresis (PFGE)"J Infect Chemother. 8. 353-358 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Konishi E: "Dengue type 2 virus subviral extracellular particles produced by a stably transfected mammalian cell line and their evaluation for a subunit vaccine"Vaccine. 20. 1058-1067 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Naoi K: "A new approach for the analysis of seroprevalence data : a mathematical analysis of the seroprevalence of Toxoplasma gondii infection in Hyogo prefecture (Japan) with an implication of periodic outbreaks among young children"Japanese Journal of Tropical Medicine and Hygiene. 30. 99-102 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Konishi E: "Ratios of subclinical to clinical Japanese encephalitis (JE) virus infections in vaccinated populations : evaluation of an inactivated JE vaccine by comparing the ratios with those in unvaccinated populations"Vaccine. 21. 98-107 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] 奥宮明子, 片岡陳正, 小西英二: "セリンプロテアーゼのセンダイウイルス活性化作用と小分子インヒビターによるその阻害"神戸大学医学部保健学科紀要. 18. 143-148 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Osawa K, Nakajima M, Kataoka N, Arakawa S, Kamidono S: "Evaluation of antibacterial efficacy of drugs for urinary tract infections by genotyping based on pulsed-field gel electrophoresis (PFGE)"J Infect Chemother. 8. 353-357 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Eiji Konishi, Atsuko Fujii: "Dengue type 2 virus subviral extracellular particles produced by a stably transfected mammalian cell line and their evaluation for a subunit vaccine"Vaccine. 20. 1058-1067 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Koji Naoi, Eiji Konishi, Takeo Matsumura, Akihiko Yano: "A new approach for the analysis of seroprevalence data : a mathematical analysis of the seroprevalence of Toxoplasma gondli infection in Hyogo prefecture (Japan) with an implication of periodic outbreaks among young children"Japanese Journal of Tropical Medicine and Hygiene. 30. 99-102 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Eiji Konishi, Tomoyuki Suzuki: "Ratios of subclinical to clinical Japanese encephalitis (JE) virus infections in vaccinated populatipns : evaluation of an inactivated JE vaccine by comparing the ratios with those in unvaccinated populations"Vaccine. 21. 98-107 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] 1.Tada M, tsuda Y, Wanaka K, Hijikata-Okunomiya A, Hone N, Okamoto U, Okamoto S, Okada Y: "Isolation of plasma kallikrein by highly efficiency affinity chromatography and its characterization"Biol Pharm Bull. 24(5). 520-524 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] 2.Tomoo K, Satoh K, Wanaka K, Okamoto S, Hijikata-Okunomiya A, Okada Y, Ishida T: "Binding diversity of a noncovalent-type low molecular weight serine protease inhibitor and function of a catalytic water molecule : X-ray crystal structure of PKSI-527-inhibited trypsin"J Biochem. 129. 455-460 (2001)

    • Related Report
      2001 Annual Research Report

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Published: 2001-04-01   Modified: 2016-04-21  

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