Basic studies on design of artificial chemical language compounds for cell-to-cell communication in Gram-negative bacteria.

• Project/Area Number: 16580060
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Applied microbiology
• Research Institution: HIROSHIMA UNIVERSITY
• Principal Investigator: KATO Junichi Hiroshima University, Graduate School of Advanced Sciences of Matter, Professor, 大学院・先端物質科学研究科, 教授 (90231258)
• Project Period (FY): 2004 – 2005
• Project Status: Completed (Fiscal Year 2005)
• Budget Amount: ¥3,700,000 (Direct Cost: ¥3,700,000); Fiscal Year 2005: ¥1,000,000 (Direct Cost: ¥1,000,000); Fiscal Year 2004: ¥2,700,000 (Direct Cost: ¥2,700,000)
• Keywords: quorum sensing / cell-to-cell communication / acyl homoserine lactone / Pseudomonas aeruginosa / artificial chemical language compounds / アシル化ホモセリンラクトン / オートインデューサー / クゥオーラムセンシング / 緑膿菌 / 化学言語 / 病原因子 / バイオフィルム

Research Abstract

Many Gram-negative bacteria communicate with each other by using N-acyl-L-homoserine lactone (AHL) as "chemical language"". This cell-to-cell communication is called quorum sensing. We synthesized a series of AHL analogs and tested them for functioning as "chemical language". It was found that N-acyl-cyclopentylamides show inhibitory effects on quorum sensing in Pseudomonas aeruginosa. N-Decanoylcyclopentylamide (C10-CPA) is the strongest antagonist among N-acylcyclopentylamides synthesized. C10-CPA inhibits production of pathogenic factors including elastase, rhamnolipid, and pyocyanin as well as biofilm formation in P.aeruginosa.. Genetic analysis suggested that C10-CPA inhibits enzymatic activity of LasI, which synthesizes AHL. LasR and RhlR, which are regulatory proteins in quorum sensing, are thought to be important for evaluating synthesized compounds as artificial chemical languages. We successfully overexpressed the lasR and rhlR genes in Escherichia coli and purified them. We also confirmed that purified LasR and RhlR retain the ability to bind to their cognate DNA binding sites.

Research Products

• [Journal Article] Control of quorum sensing systems in Pseudomonas aeruginosa by acyl homoserine lactone analogues. (2004)
  • Author(s): Takenori Ishida, et al.
  • Journal Title: Conference Proceedings of The 10^<th> APCChE Congress Pages: 301-53
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Quorum sensing control using autoinducer homologues and cyclo-dexstrin in Gram-negative bacteria. (2004)
  • Author(s): Tsukasa Ikeda, et al.
  • Journal Title: Conference Proceedings of The 10^<th> APCChE Congress
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Control of quorum sensing systems in Pseudomonas aeruginosa by acyl homoserine lactone analogues. (2004)
  • Author(s): Takenori Ishida, et al.
  • Journal Title: Conference Proceedings of the 10^<th> APCChE Congress 3P-01-053(CD-ROM)
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Quorum sensing control using autoinducer homologues and cyclodexstrin in Gram-negative Bactira. (2004)
  • Author(s): Tsukasa Ikeda, et al.
  • Journal Title: Conference Proceedings of the 10^<th> APCChE Congress 2L-11(CD-ROM)
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Control of Quorum Sensing Systems in Pseudomonas aeruginosa by Acyl Homoserine Lactone Analogues (2004)
  • Author(s): Ishida, T., Kuroda, A., Takiguchi, N., Ohtake, H., Kato, J., Ikeda, T.
  • Journal Title: The 10th APCChE congress, Conference Proceedings 3P-01-086(CD-ROM) Pages: 1-7