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Establishment of New Strategy for Treatment of Pseudomonal Infection with Genes Requiring Susceptibility of Antibiotic Agents

Research Project

Project/Area Number 16590755
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Respiratory organ internal medicine
Research InstitutionHospital of Medicine and Dentistry

Principal Investigator

HIGASHIYAMA Yasuhito  Nagasaki University Hospital, Medicine and Dentistry, Assistant Professor, 医学部・歯学部附属病院, 講師 (30304926)

Co-Investigator(Kenkyū-buntansha) KOHNO Shigeru  Nagasaki University, Graduate School of Biomedical Sciences, Professor, 大学院・医歯薬学総合研究科, 教授 (80136647)
Project Period (FY) 2004 – 2005
Project Status Completed (Fiscal Year 2005)
Budget Amount *help
¥2,900,000 (Direct Cost: ¥2,900,000)
Fiscal Year 2005: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 2004: ¥2,200,000 (Direct Cost: ¥2,200,000)
KeywordsPseudomonas aeruginosa / outer membrane / quorum sensing system / Macrolide / Pseudomonas quinolone signal / transposon / 定数増殖期 / quorum-sensing system / マクロライド / アジスロマイシン
Research Abstract

Treatment of Pseudomonas aeruginosa infection is full of difficulty due to drug resistance of the organism. However, the macrolide, which shows no antibacterial activity to P.aeruginosa, is effective for treatment of patients with chronic pseudomonal respiratory tract infection. We discovered that macrolide had bactericidal effect in stationary growth phase in P.aeruginosa. NPN, fluorescent probe, assay proved that azithromycin, a macrolide, interact to outermembrane of the organism. In addition, I found that the macrolide sensitivity depended on quorum sensing system (QS system) of P.aeruginosa and identified the gene, which was controlled by this QS system and was related to macrolide sensitivity. In result, expression of the pqsA-E operon, which was one of Pseudomonas qquinolone signal (PQS) biosynthesis genes, was required for macrolide susceptibility. Next, to clarify expression mechanism of the operon, we established a mutant that had insertion of pqsA'-lacZ fusion on it's chromosome and made a random transposon mutant library of the mutant. We identified 27 genes, which related pqsA-E operon expression. Genes related to flagellum, cell division, nucleotide biosynthesis, metabolism, drug and, PQS biosynthesis genes (pqsA, pqsB, pqsC, pqsD, pqsH, pqsR) were included. These results suggested that macrolide-susceptibility in stationary growth phase may required activation of those genes

Report

(3 results)
  • 2005 Annual Research Report   Final Research Report Summary
  • 2004 Annual Research Report
  • Research Products

    (3 results)

All 2005

All Journal Article (3 results)

  • [Journal Article] Azithromycin exhibits bactericidal effects on Pseudomonas aeruginosa through interaction with the outer membrane2005

    • Author(s)
      Imamura Y, Higashiyama Y, Tomono K, et al.
    • Journal Title

      Antimicrobial Agents and Chemotherapy 49・4

      Pages: 1377-80

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Annual Research Report 2005 Final Research Report Summary
  • [Journal Article] Azithromycin exhibits bactericidal effects on Pseudomonas aeruginosa through interaction with the outer membrane2005

    • Author(s)
      Imamura Y, Higashiyama Y, Tomono K, et al.
    • Journal Title

      Antimicrobial Agents and Chemotherapy 49

      Pages: 1377-1380

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Azithromycin exhibits bactericidal effects on Pseudomonas aeruginosa through interaction with the outer membrane2005

    • Author(s)
      Imamura Y, Higashiyama Y, Tomono K, et al.
    • Journal Title

      Antimicrobial Agents and Chemotherapy 49・4(印刷中)

    • Related Report
      2004 Annual Research Report

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Published: 2004-04-01   Modified: 2016-04-21  

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