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

用于革兰氏阴性细菌细胞间通讯的人工化学语言化合物设计的基础研究。

• 批准号: 16580060
• 负责人: KATO Junichi
• 金额: $ 2.37万
• 依托单位: HIROSHIMA UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2004
• 资助国家: 日本
• 起止时间: 2004 至 2005
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-16580060/
• 关键词: 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

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.

许多革兰氏阴性细菌通过使用N-酰基-L-高丝氨酸内酯（AHL）作为“化学语言”来相互交流。这种细胞与细胞之间的交流称为群体感应。我们合成了一系列AHL类似物并测试了它们作为“化学语言”的功能。发现N-酰基环戊酰胺对假单胞菌中的群体感应表现出抑制作用 铜绿假单胞菌。 N-癸酰环戊酰胺 (C10-CPA) 是合成的 N-酰基环戊酰胺中最强的拮抗剂。 C10-CPA 抑制铜绿假单胞菌中弹性蛋白酶、鼠李糖脂和绿脓素等致病因子的产生以及生物膜的形成。遗传分析表明，C10-CPA 抑制 LasI 的酶活性，可合成 AHL。 LasR 和 RhlR 是群体感应中的调节蛋白，被认为对于评估合成化合物作为人工化学语言非常重要。我们成功在大肠杆菌中过表达 lasR 和 rhlR 基因并进行纯化。我们还证实纯化的 LasR 和 RhlR 保留与其同源物结合的能力 DNA 结合位点。

项目成果

Quorum sensing control using autoinducer homologues and cyclo-dexstrin in Gram-negative bacteria.

在革兰氏阴性细菌中使用自诱导剂同系物和环糊精进行群体感应控制。

• 发表时间: 2004
• 期刊: Conference Proceedings of The 10^<th> APCChE Congress
• 作者: Tsukasa Ikeda;et al.
• 通讯作者: et al.

Control of quorum sensing systems in Pseudomonas aeruginosa by acyl homoserine lactone analogues.

通过酰基高丝氨酸内酯类似物控制铜绿假单胞菌中的群体感应系统。

• 发表时间: 2004
• 期刊: Conference Proceedings of The 10^<th> APCChE Congress
• 作者: Takenori Ishida;et al.
• 通讯作者: et al.

Quorum sensing control using autoinducer homologues and cyclodexstrin in Gram-negative Bactira.

在革兰氏阴性杆菌中使用自诱导剂同系物和环糊精进行群体感应控制。

• 发表时间: 2004
• 期刊: Conference Proceedings of the 10^<th> APCChE Congress 2L-11(CD-ROM)
• 作者: Tsukasa Ikeda;et al.
• 通讯作者: et al.

Control of Quorum Sensing Systems in Pseudomonas aeruginosa by Acyl Homoserine Lactone Analogues

酰基高丝氨酸内酯类似物对铜绿假单胞菌群体感应系统的控制

• 发表时间: 2004
• 期刊: The 10th APCChE congress, Conference Proceedings 3P-01-086(CD-ROM)
• 作者: Ishida;T.;Kuroda;A.;Takiguchi;N.;Ohtake;H.;Kato;J.;Ikeda;T.
• 通讯作者: T.