Development of novel anti-microbial drugs targeting quorum sensing in Gram-positive bacteria
| Project/Area Number |
17580068
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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 UNIVERCITY |
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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, Associate Professor, 大学院農学生命科学研究科, 助教授 (30280788)
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| Project Period (FY) |
2005 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥3,700,000 (Direct Cost: ¥3,700,000)
Fiscal Year 2006: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2005: ¥2,700,000 (Direct Cost: ¥2,700,000)
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| Keywords | Enterococcus faecalis / Quorum sensing / Screening / Inhibitor / Gelatinase / Virulence factor / Anti-pathogenic compound / Post-antibiotics |
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| 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.
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Report
(3 results)
Research Products
(11 results)
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[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
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Journal Title
J.Bacteriol. 189(4)
Pages: 1358-1365
Description
「研究成果報告書概要(欧文)」より
Related Report
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[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
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Journal Title
J.Bacteriol. 188(23)
Pages: 8321-8326
Description
「研究成果報告書概要(欧文)」より
Related Report
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