| Project/Area Number |
15580065
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Applied microbiology
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| Research Institution | KYUSHU UNIVERSITY |
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Principal Investigator |
NAKAYAMA Jiro Kyushu University, Faculty of Agriculture, Associate Professor, 農学研究院, 助教授 (40217930)
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| Co-Investigator(Kenkyū-buntansha) |
NAGATA Koji The University of Tokyo, Graduate School of Agricultural and Life Sciences, Research Associate, 大学院・農学生命科学研究科, 助手 (30280788)
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| Project Period (FY) |
2003 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥3,800,000 (Direct Cost: ¥3,800,000)
Fiscal Year 2004: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2003: ¥2,700,000 (Direct Cost: ¥2,700,000)
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| Keywords | Enterococcus faecalis / quorum sensing / screening / inhibitor / gelatinase / virulence factor / anti-infectious substance / post-antibiotics / クオーラムセンシング / ポスト坑成物質 / 環状ペプチドフェロモン / 自己誘導ペプチド / アンタゴニスト / 病原性プロテアーゼ |
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| Research Abstract |
Inhibitors targeting bacterial quorum sensing system offer a novel means of treating virulent and/or antibiotic resistant infections and quorum sensing researches in vivo or in vitro. The expression of two Enterococcus faecalis virulence-related proteases, gelatinase and serine protease, is positively regulated by a quorum sensing system encoded by fsr gene cluster. Recent studies have suggested that the fsr system is involved in biofilm formation and others more than the protease production. In the present study, we screened for quorum sensing inhibitors targeting fsr regulatory system from actinomycetes secondary metabolites. E.faecalis was cultured with each tested actinomycetes culture supernatant and the productions of gelatinase and GBAP(gelatinase biosynthesis activating pheromone) were tested for the first and second screenings, respectively. Culture supernatant of Streptomyces sp. QI-Y33-1 showed most potent inhibitory effect on both gelatinase and GBAP productions without inhibiting E.faecalis cell growth. The active compound named Y33-1 was isolated from the culture supernatant. Y33-1 suppressed both gelatinase and GBAP productions at submicromolar concentrations, whereas inhibiting E.faecalis cell growth at concentrations above ten micromolar. Y33-1 also suppressed gelatinase production of E.faecalis when biological or higher concentrations of synthetic GBAP was added to the culture, suggesting that Y33-1 inhibited the signal transduction of GBAP via fsr system. The structure analysis of Y33-1 and further screening for fsr inhibitors are now under progress as well as the investigation of the possibility of chemotherapy by using Y33-1.
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