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2006 Fiscal Year Final Research Report Summary

Development of novel anti-microbial drugs targeting quorum sensing in Gram-positive bacteria

Research Project

Project/Area Number 17580068
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Applied microbiology
Research InstitutionKYUSHU UNIVERCITY

Principal Investigator

NAKAYAMA Jiro  Kyushu University, Faculty of Agriculture, Associate Professor, 農学研究院, 助教授 (40217930)

Co-Investigator(Kenkyū-buntansha) NAGATA Koji  The University of Tokyo, Graduate School of Agricultural and Life Sciences, Associate Professor, 大学院農学生命科学研究科, 助教授 (30280788)
Project Period (FY) 2005 – 2006
KeywordsEnterococcus faecalis / Quorum sensing / Screening / Inhibitor / Gelatinase / Virulence factor / Anti-pathogenic compound / Post-antibiotics
Research Abstract

The expression of two Enterococcus feacalis virulence-related proteases, gelatinase and serine protease, is positively regulated by a quorum sensing system encoded by the fsr gene cluster. In this system, E. feacalis secretes an autoinducing peptide, gelatinase biosynthesis-activating pheromone(GBAP), which triggers the FsrC-FsrA two component regulatory system controlling the expression of two transcripts, fsrBDC and gelE-sprE. To aim anti-pathogenic compounds targeting cyclic peptide-mediated quorum sensing in Gram-positive bacteria, we have studied on (1) biosynthetic molecular mechanism of cyclic peptide quormone 'GBAP' and (2) screening for inhibitors of GBAP-mediated quorum sensing 'fir regulatory system'.
(1) In this study, we demonstrated the existence offsrD, encoding the GBAP propeptide, which is in frame with fsrB but is translated independently of fsrB. It was also demonstrated that FsrB', an FsrD-truncated FsrB, functions as a cysteine protease-like processing enzyme to generate GBAP from FsrD. This revised model is consistent with the staphylococcal agr system.
(2) We have screened for inhibitors of the fsr quorum sensing from actinomycetes metabolites, and identified a known peptide antibiotic, siamycin I. Quantitative analysis offsrBDC and gelE-sprE transcript suggested that siamycin I inhibited the GBAP-signaling via FsrC-FsrA two component regulatory system in a noncompetitive maner. The sublethal concentration of siamysin I also attenuated biofilm formation. Overrall, siamycin I would offer a novel means of treating enterococcal infections.

  • Research Products

    (6 results)

All 2007 2006

All Journal Article (6 results)

  • [Journal Article] Siamycin attenuates fsr quorum sensing mediated by gelatinase biosynthesis-activating pheromone in Enterococcus faecalis2007

    • Author(s)
      J.Nakayama et al.
    • Journal Title

      Journal of Bacteriology 189・4

      Pages: 1358-1365

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Siamycin attenuates fsr quorum sensing mediated by gelatinase biosynthesis-activating pheromone in Enterococcus faecalis2007

    • Author(s)
      Nakayama, J., E.Tanaka, R.Kariyama, K.Nagata, K.Nishiguchi, R.Mitsuhata, Y.Uemura, M.Tanokura, H.Kumon, K.Sonomoto
    • Journal Title

      J.Bacteriol. 189(4)

      Pages: 1358-1365

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Revised model for Enterococcus faecalis fsr quorum-sensing system : small open reading frame, fsrD, encodes gelatinase biosynthesis-activating pheromone propeptide corresponding to staphylococcal AgrD2006

    • Author(s)
      J.Nakayama et al.
    • Journal Title

      Journal of Bacteriology 188・23

      Pages: 8321-8326

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] 腸球菌のfsr制御系を標的としたクォーラムセンシング阻害剤開発2006

    • Author(s)
      西口賢三ら
    • Journal Title

      生物工学 84・10

      Pages: 440-443

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Revised model for Enterococcus faecalis fsr quorum-sensing system : small open reading frame, fsrD, encodes gelatinase biosynthesis-activating pheromone propeptide corresponding to staphylococcal AgrD2006

    • Author(s)
      Nakayama, J., S.Chen, N.Oyama, K.Nishiguchi, E.A.Azab, E.Tanaka, R.Kariyama, K.Sonomoto
    • Journal Title

      J.Bacteriol. 188(23)

      Pages: 8321-8326

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Development of qorum sensing inhibitors targeting enterococcal fsr system2006

    • Author(s)
      Nishiguchi, K., J.Nakayama, K.Sonomoto
    • Journal Title

      Seibutsu-kougaku Kaishi 84(10)

      Pages: 440-443

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 2008-05-27  

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