薬剤耐性肺炎球菌のin vivo MS解析とキューブ型DNA抗菌薬の開発研究

耐药肺炎球菌体内MS分析及立方体DNA抗生素的开发研究

• 批准号: 20H03858
• 负责人: 寺尾 豊
• 金额: $ 11.48万
• 依托单位: Niigata University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2020
• 资助国家: 日本
• 起止时间: 2020-04-01 至 2024-03-31
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-20H03858/
• 关键词: 肺炎球菌; Streptococcus pneumoniae

新型コロナウイルスの流行で，数多くの感染者，重症肺炎患者および死者が発生し，患者個々の健康問題だけでなく，社会・経済・医療システム全般に大きな負の影響が生じている．また，新型コロナウイルス性肺炎を除いても，国内では年間に約13万人もの肺炎死者（誤嚥性肺炎を含む）が報告され，かつ増加し続けている．本課題の基盤B研究では，耐性肺炎球菌による肺炎の重症化機構をin vivo解析し，耐性菌による肺炎の治療基盤を構築することを目的に掲げた．具体的には，耐性肺炎球菌の肺感染マウス系を確立後，肺胞中の耐性菌とマウスの両分子群をiTRAQ-MS/MS法で網羅同定した後，耐性菌とマウスの両分子群の動態を多分子同時解析装置で詳細分析した．そして，肺炎の重症化に関与する分子を治療標的として選出し，当時採択さてれていた萌芽研究のin vitro系で確立し 特許出願したDNAの立体化技術を用い，in vivo系において耐性肺炎球菌の病原因子のみを特異的に制御する抗菌薬の開発を期した．その結果，当初4ヵ年計画の3年目の現在までに，研究成果の英語学術論文19篇（そのうち責任著者が10篇）の発表および成果特許1件を出願し，当初計画以上の科研費研究の遂行実績を挙げることができている（詳細はJSTの“researchmap”に記載済み）．2019年12月末に発生した新型コロナウイルスの影響により，研究組織全員のモチベーションと責任感が高まったことに加え，感染症研究の各種試薬や実験機器が世界的に充実した点も大きいと考察している．さらに，本研究では代表者と全ての分担者が，それぞれ大学院生を育成しながら計画を推進した．耐性菌に関する基礎研究もその専門人材養成も，「薬剤耐性AMRアクションプラン」において日本政府が決定した政策であり，教育貢献かつ社会貢献の意義も高いと考えられた．

The number of people infected with severe pneumonia, the number of people infected with severe pneumonia, the health problems of the patients, the health problems of the patients, In China, there are about 130000 people who died of pneumonia (including typhoid pneumonia) every year. In China, there are about 130000 people who have died of pneumonia (including typhoid pneumonia). This topic is based on the basic study, the in vivo analysis of the mechanism for the severity of pneumonia caused by resistant pneumococcal pneumonia, the treatment of pneumonia by resistant bacteria, the treatment of pneumonia, and the purpose of the treatment of pneumonia. the purpose of this study is to determine the details of the study. After the confirmation of the resistant pneumococcal lung infection strain, the molecular group of the resistant bacteria in the lung cell was identified by iTRAQ-MS/MS method, and the molecular group of the resistant bacteria was identified by the iTRAQ-MS/MS method. The multi-molecule simultaneous analysis device was used to analyze the symptoms of severe pneumonia and the molecular treatment of pneumonia. The in vitro system has established a special program for the use of three-dimensional technology of DNA, and in vivo has been specially designed to control the start-up period of the pathogen of resistant pneumococcal pneumococci. Results, the results of the first 4 years plan and 3 years are now in progress. The research results have been published in 19 papers on English science and technology (10 of which have been published by many authors). There is a special report on one of the above scientific research results. It was originally planned that the above-mentioned scientific research projects were successfully completed. The results of the study were published in the JST "researchmap" records. At the end of December, 2019, there was a significant impact on the new type of scientific research. All members of the research organization have been involved in the study of infectious diseases. All members of the research organization have been involved in the study of infectious diseases. in this study, all members of the research organization have been invited to participate in the study of infectious diseases, the study of infectious diseases, the study of all kinds of infectious diseases, the study of infectious diseases, and the study of infectious diseases. The Japanese government has decided to make a decision on AMR policy, education and social contribution, which means higher education, higher education and higher education.

项目成果

エリスロマイシンのDel-1誘導による骨免疫制御作用の解析

Del-1诱导红霉素骨免疫调节作用分析

• 发表时间: 2021
• 作者: 田村 光;土門久哲;日吉 巧;前田健康;多部田康一;寺尾 豊;前川知樹
• 通讯作者: 前川知樹

Degradation of EGFR on lung epithelial cells by neutrophil elastase contributes to the aggravation of pneumococcal pneumonia.

中性粒细胞弹性蛋白酶在肺上皮细胞上降解会导致肺炎球菌肺炎的加剧。

• DOI: 10.1016/j.jbc.2023.104760
• 发表时间: 2023-06
• 期刊: JOURNAL OF BIOLOGICAL CHEMISTRY
• 影响因子: 4.8
• 作者: Isono, Toshihito;Hirayama, Satoru;Domon, Hisanori;Maekawa, Tomoki;Tamura, Hikaru;Hiyoshi, Takumi;Sirisereephap, Kridtapat;Takenaka, Shoji;Noiri, Yuichiro;Terao, Yutaka
• 通讯作者: Terao, Yutaka

身の回りのウイルスや細菌について．

关于我们周围的病毒和细菌。

• 发表时间: 2021
• 作者: 池田弘;永松有紀;清水博史;寺尾 豊
• 通讯作者: 寺尾 豊

Clarithromycin Inhibits Pneumolysin Production via Downregulation of ply Gene Transcription despite Autolysis Activation.

• DOI: 10.1128/spectrum.00318-21
• 发表时间: 2021-10-31
• 期刊: Microbiology spectrum
• 影响因子: 3.7
• 作者: Domon H;Isono T;Hiyoshi T;Tamura H;Sasagawa K;Maekawa T;Hirayama S;Yanagihara K;Terao Y
• 通讯作者: Terao Y

The Proinflammatory Cytokine IL-36γ Is a Global Discriminator of Harmless Microbes and Invasive Pathogens within Epithelial Tissues.

• DOI: 10.1016/j.celrep.2020.108515
• 发表时间: 2020-12-15
• 期刊: Cell reports
• 影响因子: 8.8
• 作者: Macleod T;Ainscough JS;Hesse C;Konzok S;Braun A;Buhl AL;Wenzel J;Bowyer P;Terao Y;Herrick S;Wittmann M;Stacey M
• 通讯作者: Stacey M