Study on bacterial gene expression activated in host and regulation of phagocytosis-mediated infectious diseases

• Project/Area Number: 17K07331
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Functional biochemistry
• Research Institution: Sapporo Medical University (2018-2020); Kanazawa University (2017)
• Principal Investigator: Shiratsuchi Akiko 札幌医科大学, 医療人育成センター, 教授 (90303297)
• Project Period (FY): 2017-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: 自然免疫 / 感染症 / 細菌 / 二成分制御系 / 宿主 / 遺伝子発現 / シグマ因子 / 低分子RNA / 細菌宿主共存 / 大腸菌 / 細胞貪食 / 食細胞 / 発現制御

Outline of Final Research Achievements

Bacteria under hostile environmental conditions change their gene expression with aid of the two-component system (TCS), a bacterial signaling system, to adapt and survive in the host. This study identified several genes coding TCS factors acted for regulation of bacterial virulence. EnvZ-OmpR regulated one gene that codes membrane-located protein to enhance host-killing activity through altering level of unknown virulence factor in bacteria.

Academic Significance and Societal Importance of the Research Achievements

細菌感染は他の多くの疾患のリスク因子であり，感染症のみならず全身性の疾患の理解に必須となってきている。また，細菌の中には実験室環境では強い毒性を持たないにもかかわらず，重篤な感染症を引き起こす種類も存在する。細菌には環境を感知して遺伝子発現を変化させる仕組みがあることから，宿主内で発現変動して毒性を調節し，細菌も宿主も死なないようにして感染を続ける機構が細菌に備わっている可能性がある。本研究では，そのように働く受容体と実行因子遺伝子を同定した。当該受容体を標的として，化合物や天然物，あるいは承認薬の中から，新たな考えに基づいた医薬品や抗菌商品に繋がるものが見出される可能性がある。

Research Products

• [Int'l Joint Research] ハサヌディン大学(インドネシア)
• [Int'l Joint Research] 釜山大学/ソウル大学(韓国)
• [Int'l Joint Research] カロリンスカ研究所(スウェーデン)
• [Int'l Joint Research] 釜山大学/ソウル大学(韓国)
• [Int'l Joint Research] ハサヌディン大学(インドネシア)
• [Int'l Joint Research] カロリンスカ研究所/ウメオ大学(スウェーデン)
• [Int'l Joint Research] 釜山大学/ソウル大学(韓国)
• [Int'l Joint Research] ハサヌディン大学(インドネシア)
• [Int'l Joint Research] カロリンスカ研究所(スウェーデン)
• [Int'l Joint Research] ソウル大学/釜山大学(韓国)
• [Int'l Joint Research] ハサヌディン大学(インドネシア)
• [Journal Article] Using Drosophila to study the mechanisms of cancer development and prevention. (2021)
  • Author(s): Nagaosa K & Shiratsuchi A
  • Journal Title: J. Cent. Med. Edu. Sapporo Medical University Volume: 12 Pages: 9-16
  • NAID: 40022513751
  • Peer Reviewed / Open Access
• [Journal Article] Role for phagocytosis in the prevention of neoplastic transformation in Drosophila (2020)
  • Author(s): Zhang Min、Nagaosa Kaz、Nakai Yuji、Yasugi Tetsuo、Kushihiki Masako、Rahmatika Dini、Sato Makoto、Shiratsuchi Akiko、Nakanishi Yoshinobu
  • Journal Title: Genes to Cells Volume: 25 Issue: 10 Pages: 675-684
  • DOI: 10.1111/gtc.12804
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Fruit fly as a model organism in the study of human diseases and drug discovery (2019)
  • Author(s): Nainu F, Nakanishi Y & Shiratsuchi A
  • Journal Title: 札幌医科大学医療人育成センター紀要 = Journal of center for medical education Sapporo Medical University = Journal of center for medical education Sapporo Medical University Volume: 10 Pages: 21-32
  • DOI: 10.15114/jcme.10.21
  • NAID: 120006647837
  • URL: https://sapmed.repo.nii.ac.jp/records/14061
  • Year and Date: 2019-03-31
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Protective effects of Phaseolus vulgaris lectin against viral infection in Drosophila. (2017)
  • Author(s): Ekowati H, Arai J, Damana Putri AS, Nainu F, Shiratsuchi A, Nakanishi Y.
  • Journal Title: Drug Discov Ther. Volume: 11 Pages: 329-335
  • NAID: 130006308080
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Mechanisms and Significance of Phagocytic Elimination of Cells Undergoing Apoptotic Death (2017)
  • Author(s): Nonaka, S., Shiratsuchi, A., Nagaosa, K., and Nakanishi, Y.
  • Journal Title: Biological and Pharmaceutical Bulletin Volume: 40 Issue: 11 Pages: 1819-1827
  • DOI: 10.1248/bpb.b17-00478
  • NAID: 130006191964
  • ISSN: 0918-6158, 1347-5215
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Induction of Apoptosis and Subsequent Phagocytosis of Virus-Infected Cells As an Antiviral Mechanism. (2017)
  • Author(s): Nainu F, Shiratsuchi A, Nakanishi Y.
  • Journal Title: Front Immunol. Volume: 8 Pages: 1220-1220
  • DOI: 10.3389/fimmu.2017.01220
  • NAID: 120006370948
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Signaling pathway for phagocyte priming upon encounter with apoptotic cells. (2017)
  • Author(s): Nonaka S, Ando Y, Kanetani T, Hoshi C, Nakai Y, Nainu F, Nagaosa K, Shiratsuchi A, Nakanishi Y.
  • Journal Title: J Biol Chem. Volume: 292 Pages: 8059-8072
  • NAID: 120006336006
  • Peer Reviewed / Int'l Joint Research
• [Presentation] 細胞膜受容体を介した宿主毒性制御 (2020)
  • Author(s): 白土明子
  • Organizer: 第９３回日本生化学会大会 シンポジウム
  • Invited
• [Presentation] 貪食受容体による癌予防に関する研究 (2020)
  • Author(s): 永長一茂，張敏，西千恵子，中井雄治，白土明子，中西義信
  • Organizer: 日本生化学会東北支部第86回例会・シンポジウム
• [Presentation] タバコ成分による大腸菌の遺伝子発現制御系活性への影響 (2019)
  • Author(s): 白土明子，有木茂，木戸浦悠人，長谷川浩，中西義信
  • Organizer: 第42回日本分子生物学会年会
• [Presentation] Regulation of bacterial virulence in infectious condition (2019)
  • Author(s): Akiko Shiratsuchi
  • Organizer: Symposium of the European Network for Aggregatibacter actinomycetemcomitans Research 2019年9月25日 The European Network for Aggregatibacter actinomycetemcomitans Research 招待有り
  • Int'l Joint Research / Invited
• [Presentation] 宿主感染時の大腸菌の毒性抑制機構 (2019)
  • Author(s): 白土明子，山下哲，天笠雄太，小宮山千晴，成田知也，山本兼由，石浜明，中西義信
  • Organizer: 第92回生化学会大会
• [Presentation] 宿主感知による細菌の遺伝子発現変動と宿主との共存 (2019)
  • Author(s): 白土明子
  • Organizer: 2019年度日本生化学会北海道支部例会
  • Invited
• [Presentation] 細菌の混合感染による宿主毒性の制御 （和訳） (2019)
  • Author(s): Akiko Shiratsuchi
  • Organizer: ウメオ大学歯学部セミナー
  • Int'l Joint Research / Invited
• [Presentation] ショウジョウバエ遺伝学を用いた疾患モデル研究の展開 (2019)
  • Author(s): 白土明子
  • Organizer: 札幌医科大学病態生理リサーチカンファレンス
  • Invited
• [Presentation] Role for outer membrane protein OmpC on Escherichia coli virulence for control infection in host. (2018)
  • Author(s): Shiratsuchi A, Amagasa Y, Yamashita S & Nakanishi Y.
  • Organizer: 3rd Asian Invertebrate Immunity Symposium
  • Int'l Joint Research
• [Presentation] 細菌の宿主環境の感知による感染制御機構 (2018)
  • Author(s): 白土明子
  • Organizer: 2017年度日本薬学会第138年会. シンポジウム「生物の環境認識メカニズムの理解と応用への可能性」（金沢）
  • Invited
• [Presentation] 大腸菌二成分制御系による宿主感染と傷害の調節． (2017)
  • Author(s): 白土明子
  • Organizer: 2017年度生命科学系学会合同年次大会 第40回日本分子生物学会年会・日本生化学会第90回大会合同大会．ワークショップ「環境変化とそれに応答する細胞内変化の再発見」（神戸）
  • Invited
• [Presentation] Transcriptional control of bacterial genes in host organism: role for two-component system in infection diseases. (2017)
  • Author(s): Shiratsuchi, A
  • Organizer: Seoul National University School of Density Symposium on Infection and Immunity.（韓国）
  • Int'l Joint Research / Invited
• [Presentation] Role for two-component regulatory system in virulence control of bacteria. (2017)
  • Author(s): Shiratsuchi, A.
  • Organizer: The third Makassar Ingernational Symposium on Pharmaceutical Sciences.（インドネシア）
  • Int'l Joint Research / Invited
• [Presentation] 細菌の環境感知と感染の調節． (2017)
  • Author(s): 白土明子
  • Organizer: 日本農芸化学会東北支部シンポジウム「多様な広がりで魅せる微生物研究」．（弘前）
  • Invited