Toward development of novel medicines for bacterial infection : Search of biological functions and elucidation of mechanism on occurrence of the functions of c-di-GMP and related compounds

致力于细菌感染新药的开发：c-di-GMP及相关化合物的生物学功能探索及功能发生机制的阐明

• 批准号: 20350076
• 负责人: HAYAKAWA Yoshihiro
• 金额: $ 12.56万
• 依托单位: Aichi Institute of Technology (2009-2011)Nagoya University (2008)
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2008
• 资助国家: 日本
• 起止时间: 2008 至 2011
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-20350076/
• 关键词: 核酸・蛋白質・糖化学; 環状ビス(3'-5')ジグアニル酸; バイオフィルム; 免疫; 薬剤耐性菌; ワクチン; 環状ジグアニル酸; 免疫活性化; インターフェロン; 機能性タンパク質; STING; バイオフィルム感染症; 環状ビス(3' -5')ジグアニル酸; 細菌感染症; 免疫賦活剤; アジュバント; メチシリン耐性黄色ブドウ球菌; 抗がん作用; 環状ジグアリル酸; 感染症治療薬; 免疫活性化剤; 抗がん剤; 肺炎球菌; 2'-O-TBDMS-c-di-

We have carried out this work aiming to find biological functions of cyclic bis(3'-5') diguanylic acid(c-di-GMP) and related compounds and to elucidate the mechanism on occurrence of the functions. As the result, the work has disclosed that c-di-GMP and some of its derivatives bear bioactivities, which include reduction of infection of methicillin-resistant Staphylococcus aureus(MRSA) by acting as an immunomodulator and vaccine adjuvant. Further, the work has revealed that c-di-GMP binds to stimulator of interferon genes(STING), existing in mammals, to induce immunity ; this discovery will be a keystone for elucidation of mechanism on occurrence of functions of c-di GMP and related compounds.

本研究旨在发现环二鸟苷酸（c-di-GMP）及其相关化合物的生物学功能，并阐明其生物学功能发生的机制。结果，该工作公开了c-di-GMP及其一些衍生物具有生物活性，包括通过充当免疫调节剂和疫苗佐剂来减少耐甲氧西林金黄色葡萄球菌（MRSA）的感染。此外，该工作揭示了c-di-GMP与存在于哺乳动物中的干扰素基因刺激因子（STING）结合以诱导免疫;该发现将是阐明c-di GMP和相关化合物的功能发生机制的关键。

项目成果

A host type I interferon response is induced by cytosolic sensing of the bacterial second messenger cyclic-di-GMP.

• DOI: 10.1084/jem.20082874
• 发表时间: 2009-08-31
• 期刊: The Journal of experimental medicine
• 作者: McWhirter SM;Barbalat R;Monroe KM;Fontana MF;Hyodo M;Joncker NT;Ishii KJ;Akira S;Colonna M;Chen ZJ;Fitzgerald KA;Hayakawa Y;Vance RE
• 通讯作者: Vance RE

Intact laser desorption of guanosine 5'-monophosphate facilitated by the phosphoesterification - Conformational analysis by infrared vibrational spectroscopy

磷酸酯化促进鸟苷 5-单磷酸的完整激光解吸 - 通过红外振动光谱进行构象分析

• 发表时间: 2010
• 作者: H. Asami;A. Motoda;M. Tsukamoto;Y. Hayakawa;and H. Saigusa
• 通讯作者: and H. Saigusa

C-di-GMP is an effective immuno, odulator and vaccine adjuvant against pneumococcal infection

C-di-GMP 是一种有效的抗肺炎球菌感染的免疫佐剂、调节剂和疫苗佐剂

• 发表时间: 2008
• 期刊: Vaccine
• 影响因子: 5.5
• 作者: A. D. Ogunniyi;J. P. Paton;A. C. Kieby;J. A. McCullers;J. Cook;M. Hyodo;Y. Hayakawa;and D. K. R. Karaolis
• 通讯作者: and D. K. R. Karaolis

STING is a direct innate immune sensor of cyclic dinucleotides

STING 是环状二核苷酸的直接先天免疫传感器

• 发表时间: 2011
• 期刊: Nature
• 影响因子: 64.8
• 作者: Dara L. Burdette;Kathryn M. Monroe;Katia Sotelo-Troha;Barbara Eckert;Mamoru Hyodo;Yoshihiro Hayakawa;and Russell E. Vance
• 通讯作者: and Russell E. Vance

Anaplasma phagocytophilum PleC and PleD Diguanylate Cyclase Two-Component System and Role of Cyclic Di-DMP in Host-Cell Infection

嗜吞噬细胞无形体 PleC 和 PleD 二鸟苷酸环化酶双组分系统以及环状 Di-DMP 在宿主细胞感染中的作用

• 发表时间: 2009
• 期刊: J.Bacteriology 191
• 作者: T.-H.Lai;Y.Kumagai;M.Hyodo;Y.Hayakawa;Y.Rikihisa
• 通讯作者: Y.Rikihisa