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Isolation and characterization of the inhibitors of vbacterial signal transduction

Research Project

Project/Area Number 12660089
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field 応用微生物学・応用生物化学
Research InstitutionKinki University

Principal Investigator

UTSUMI Ryutaro  Kinki University Agricultural Chemnistry,Professor, 農学部, 教授 (20151912)

Project Period (FY) 2000 – 2001
Project Status Completed (Fiscal Year 2001)
Budget Amount *help
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2001: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2000: ¥2,200,000 (Direct Cost: ¥2,200,000)
KeywordsHistidine kinase / inhibitor / signal transduction / bacteria / drug-resistance / 2成分制御系 / 細菌情報伝達 / 二成分制御系 / 抗菌剤 / ヒスチジンキナーゼ阻害剤 / 情報伝達
Research Abstract

Histidine protein kinases (HPKs) and two-component regulation are used extensively in procaryotic signal transduction processes that allow bacteria to adapt and respond to the environment. Two-component signal transduction systems are so named because at their core are two-modules, the histidine kinase and a response regulator. In response to an enviromental siganal, the kinase autophosphorylates a conserved His residue. The His-phosphate is then transferred to an aspartyl residue on the response regulator, therby altering its activity.
We focused growth essentially YycF/YycG two-component system and demonstrated in vitro that YycG-YycF of Bacillus subtilis constitute two-components system and show the high specificity of the sensor protein for the cognate phosphorylation partner. Based on inhibition of YycG (histidine protein kinase) of Bacillus subtilis, newly synthesized imidazole derivatives were serched to identify antibacterial agents. NH125, NH126, and NH127 were found to virtually inhibit the incorporation of phosphate from ATP into YycG at 50 μg/ml with IC50 of 0.6-40 μM. They have also antibacterial activity in drug-resistant Staphylococcus aureus, Enterococcus, faecallis, and Streptococcus pneumoniae with MIC 0.39-6.25 μg/Ml. Furthermore, based on inhibition of such an autophosphorylation of YycG, zerumbone derivatives were serched to identify an antibacterial agent, NH0891.([2E, 6E, 10(E/Z)]-11-Bromo-4, 4, 7-trimethyl-2, 6, 10- dodecatrienoic acid).
In this study, we have sown the useful and important way to develop a new class of antibacterial agents.

Report

(3 results)
  • 2001 Annual Research Report   Final Research Report Summary
  • 2000 Annual Research Report
  • Research Products

    (11 results)

All Other

All Publications (11 results)

  • [Publications] R.Utsumi: "Bacterial signal transduction systems for euvironmental adaptation and their inhibitors"Microbes and Enviroments. 17(in press). (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] T.Kitayama: "Chemistry of Zerumbone 2 regulation of ring bond cleavage and unique antibacterial activities of zerumbone derivatives"Biosci.Biotechnol.Biochem.. 65. 2193-2199 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] K.Yamamoto: "Antibacterial agents that inhibits histidine protein kinase yycG of Bacillus subtilis"Biosci.Biotechnol.Biochem.. 65. 2306-2310 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Utsumi, R: "Bacterial signal transduction systems for environmental adaptation and their inhibitors"Microbes and Enviroments. 17(in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Kitayama, T., R.Utsumi et al: "Chemistry of Zerumbone 2 regulation of ring bond elevage and unique antibacterial activities of zerumbone derivatives"Biosci. Biotechnol. Biochem. 65. 2193-2199 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Yamamoto, K., R. Utsumi et al.: "Antibacterial agents that inhibit histidine protein kinase YycG of Bacillus subtills"Biosci. Biotechnol. Biochem. 65. 2306-2310 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] R.Utsumi: "Bacterial signal transduction systems for environmental adaptation and their inhibitors"Microbes and Enviroments. 17(In press). (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] T.Kitayama: "Chemistry of Zerumbone 2 regulation of ring bond cleavage and unique antibacterial activities of zerumbone derivatives"Biosci. Biotechnol. Biochem.. 65. 2193-2199 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] K.Yamamoto: "Antibacterial agents that inhibits histidine protein kinase yycG of Bacillus subtilis"Biosci. Biotechnol. Biochem.. 65. 2306-2310 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] K.Yamamoto and R.Utsumi: "Identification and characterization of potent antibacterial agent, NH125 against drug-resistant bacteria"Biosci.Biotechnol.Biochem.. 64. 919-923 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] 山本兼由,内海龍太郎: "薬剤耐性菌に対する新しい戦略-情報伝達阻害"バイオサイエンスとインダストリー. 58. 260-263 (2000)

    • Related Report
      2000 Annual Research Report

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

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