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Analysis of bacterial effector proteins that negatively regulate the host ubiquitin system

Research Project

Project/Area Number 16H05189
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Bacteriology (including mycology)
Research InstitutionGifu University (2017-2018)
Osaka University (2016)

Principal Investigator

Kubori Tomoko  岐阜大学, 大学院医学系研究科, 准教授 (20397657)

Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥17,550,000 (Direct Cost: ¥13,500,000、Indirect Cost: ¥4,050,000)
Fiscal Year 2018: ¥5,980,000 (Direct Cost: ¥4,600,000、Indirect Cost: ¥1,380,000)
Fiscal Year 2017: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2016: ¥6,110,000 (Direct Cost: ¥4,700,000、Indirect Cost: ¥1,410,000)
Keywordsユビキチン / 脱ユビキチン化酵素 / レジオネラ / エフェクター / 細菌感染
Outline of Final Research Achievements

Legionella is a bacterial pathogen that transports an extraordinary amount of effector proteins into host eukaryotic cells to manipulate various cellular systems. We have identified Legionella deubiquitinases (DUBs) as negative regulators of the host ubiquitin system. LotA was found to have dual catalytic cysteine residues and to remove ubiquitin from bacterial vacuoles in the infected cells. The DUB activity of LotA contributes intracellular bacterial growth in conjunction with other bacterial ubiquitin ligases. We also identified another Legionella DUB and its cellular target. These results demonstrate that Legionella possesses multiple approaches to manipulate host ubiquitin systems for bacterial benefit.

Academic Significance and Societal Importance of the Research Achievements

病原細菌が感染を確立する上で、宿主真核細胞の持つ普遍的なタンパク質修飾系であるユビキチンシステムを操作・撹乱することは重要な戦略として理解されている。しかしながら、ユビキチン化の負の制御機構はほとんどわかっていなかった。多様なエフェクターレパートリーを持つレジオネラをモデルシステムとして複数の脱ユビキチン化酵素を同定し、その感染における役割を分子レベルで明らかにした本研究課題は、真核生物との共存の中で確立された病原細菌の巧妙な戦略の理解に飛躍的前進を与えるものである。さらに、細菌が正負両面からユビキチン系を操作する仕組みの理解は、従来とは異なる視点からの感染防御への手がかりを与えるものである。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Annual Research Report
  • 2016 Annual Research Report
  • Research Products

    (25 results)

All 2019 2018 2017 2016 Other

All Journal Article (8 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 8 results,  Open Access: 4 results,  Acknowledgement Compliant: 2 results) Presentation (13 results) (of which Int'l Joint Research: 7 results,  Invited: 6 results) Book (1 results) Remarks (3 results)

  • [Journal Article] Emerging insights into bacterial deubiquitinases2019

    • Author(s)
      Tomoko kubori, Tomoe Kitao, Hiroki Ando
    • Journal Title

      Current Opinion in Microbiology

      Volume: 47 Pages: 14-19

    • DOI

      10.1016/j.mib.2018.10.001

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Isolation of the Dot/Icm Type IV Secretion System Core Complex from Legionella pneumophila.2019

    • Author(s)
      Kubori T, Nagai H.
    • Journal Title

      Methods Mol Biol.

      Volume: 1921 Pages: 241-247

    • DOI

      10.1007/978-1-4939-9048-1_15

    • ISBN
      9781493990474, 9781493990481
    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] LotA, a Legionella deubiquitinase, has dual catalytic activity and contributes to intracellular growth.2018

    • Author(s)
      Kubori T, Kitao T, Ando H and Nagai H.
    • Journal Title

      Cell Microbiol.

      Volume: Mar 15 Issue: 7 Pages: e12840-e12840

    • DOI

      10.1111/cmi.12840

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Subversion of Host Membrane Dynamics by the Legionella Dot/Icm TypeIV Secretion System.2017

    • Author(s)
      Hilbi H, Nagai H, Kubori T, Roy CR.
    • Journal Title

      Curr Top Microbiol Immunol.

      Volume: 413 Pages: 221-242

    • DOI

      10.1007/978-3-319-75241-9_9

    • ISBN
      9783319752402, 9783319752419
    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Legionella RavZ Plays a Role in Preventing Ubiquitin Recruitment to Bacteria-Containing Vacuoles.2017

    • Author(s)
      Kubori T, Bui XT, Hubber A and Nagai H.
    • Journal Title

      Front Cell Infect Microbiol.

      Volume: 7 Pages: 384-384

    • DOI

      10.3389/fcimb.2017.00384

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Bacterial secretion system skews the fate of Legionella-containing vacuoles towards LC3-associated phagocytosis.2017

    • Author(s)
      Hubber A., Kubori T., Coban C., Matsuzawa T., Ogawa M., Kawabata T., Yoshimori T., and Nagai H.
    • Journal Title

      Sci Rep.

      Volume: 7 Issue: 1 Pages: 44795-44795

    • DOI

      10.1038/srep44795

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Isolation of the Dot/Icm Type IV Secretion System Core Complex from Legionella pneumophila for Negative Stain Electron Microscopy Studies2017

    • Author(s)
      Kubori T and Nagai H.
    • Journal Title

      bio-protocol

      Volume: 7

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Life with bacterial secretion systems.2016

    • Author(s)
      Kubori T.
    • Journal Title

      PLoS Pathog.

      Volume: 12(8) Issue: 8 Pages: e1005562-e1005562

    • DOI

      10.1371/journal.ppat.1005562

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Presentation] Manipulation of the host ubiquitin system by Legionella2019

    • Author(s)
      Tomoko Kubori
    • Organizer
      Cold Spring Harbor Asia Conference on Bacterial Infection and Host Defense
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Manipulation of the host ubiquitin system by Legionella2018

    • Author(s)
      Tomoko Kubori
    • Organizer
      ICISE, Qui Nhon, Vietnam
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] PLOS Pathogens Writing Workshop2018

    • Author(s)
      Tomoko Kubori
    • Organizer
      ICISE, Qui Nhon, Vietnam
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Legionella manipulates host cellular systems utilizing the type IV secretion system2018

    • Author(s)
      久堀智子
    • Organizer
      第 91 回日本細菌学会総会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 宿主オートファジー関連システムとレジオネラ2017

    • Author(s)
      久堀智子、Andree Hubber、Xuan Thanh Bui、永井宏樹
    • Organizer
      第 90 回日本細菌学会総会
    • Place of Presentation
      仙台国際センター展示棟(宮城県、仙台市)
    • Year and Date
      2017-03-19
    • Related Report
      2016 Annual Research Report
  • [Presentation] Manipulation of the host ubiquitin system by Legionella Deubiquitinases.2017

    • Author(s)
      Tomoko Kubori
    • Organizer
      OIST workshop: Bacterial Flagella, Injectisome and Type III Secretion Systems
    • Place of Presentation
      沖縄科学技術大学院大学 Main Campus (沖縄県、国頭郡恩納村)
    • Year and Date
      2017-03-01
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 病原細菌レジオネラによる宿主ユビキチンシステムの操作2017

    • Author(s)
      久堀智子
    • Organizer
      新学術領域「運動超分子マシナリーが織りなす調和と多様性」 生体運動研究合同班会議
    • Place of Presentation
      神戸国際会議場 国際会議室 (兵庫県、神戸市)
    • Year and Date
      2017-01-06
    • Related Report
      2016 Annual Research Report
  • [Presentation] Manipulation of the host ubiquitin system by Legionella.2017

    • Author(s)
      Tomoko Kubori
    • Organizer
      International Union of Microbiological Societies (IUMS2017)
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 宿主オートファジー関連システムとレジオネラ2017

    • Author(s)
      久堀智子
    • Organizer
      日本顕微鏡学会 第 60 回記念シンポジウム
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] Manipulation of the host ubiquitin system by Legionella Deubiquitinases.2016

    • Author(s)
      Tomoko Kubori and Hiroki Nagai
    • Organizer
      T4SS2016: Type IV secretion in Gram-Nagative and Gram-Positive Bacteria
    • Place of Presentation
      Beilngries, GERMANY
    • Year and Date
      2016-12-08
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 病原因子分泌系を介した細菌と宿主細胞の相互作用2016

    • Author(s)
      久堀智子
    • Organizer
      東京工業大学 Cell Biology Unit 第4回コロキウム
    • Place of Presentation
      東京工業大学すずかけ台キャンパス(神奈川県、横浜市)
    • Year and Date
      2016-10-21
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] Manipulation of the host ubiquitin system by Legionella Deubiquitinases.2016

    • Author(s)
      Tomoko Kubori and Hiroki Nagai
    • Organizer
      第 15 回 あわじしま感染症・免疫フォーラム
    • Place of Presentation
      淡路夢舞台国際会議場(兵庫県、淡路市)
    • Year and Date
      2016-09-06
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Manipulation of the host ubiquitin system by Legionella Deubiquitinases.2016

    • Author(s)
      久堀智子
    • Organizer
      新学術領域「運動超分子マシナリーが織りなす調和と多様性」 第 4 回領域全体会議
    • Place of Presentation
      長崎大学良順会館(長崎県、長崎市)
    • Year and Date
      2016-06-08
    • Related Report
      2016 Annual Research Report
  • [Book] Legionella Methods and Protocols Second Edition2019

    • Author(s)
      Tomoko Kubori, Hiroki Nagai
    • Total Pages
      476
    • Publisher
      Springer Nature
    • ISBN
      9781493990474
    • Related Report
      2018 Annual Research Report
  • [Remarks] Nagai lab

    • URL

      https://sites.google.com/view/nagai-lab

    • Related Report
      2018 Annual Research Report
  • [Remarks] Nagai Lab

    • URL

      https://sites.google.com/site/nagailabjp/

    • Related Report
      2017 Annual Research Report
  • [Remarks] Nagai Lab

    • URL

      http://nagailab.biken.osaka-u.ac.jp/

    • Related Report
      2017 Annual Research Report 2016 Annual Research Report

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Published: 2016-04-21   Modified: 2020-03-30  

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