Elucidating Leptospira interrogans strategies to disassemble the junctional complex

2023 Fiscal Year Final Research Report

• Project/Area Number: 21H02732
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 49050:Bacteriology-related
• Research Institution: University of the Ryukyus
• Principal Investigator: TOMA Claudia 琉球大学, 医学(系)研究科(研究院), 准教授 (40325832)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: レプトスピラ / 尿細管上皮細胞 / 細胞間接着装置

Outline of Final Research Achievements

Leptospira interrogans disseminates hematogenously to reach the target organs by disrupting the epithelial apical junctional complex (AJC). E-cadherin is a transmembrane protein of the AJCs and is critical for maintaining AJC organization and epithelial tissue barrier function. We have reported that L. interrogans induces E-cadherin endocytosis and cytoskeletal rearrangement during AJC disassembly. In this study, we combine proteomic and imaging analysis with chemical inhibition studies to demonstrate that disrupting the AJCs of epithelial cells involves the degradation of E-cadherin scaffolding proteins, p0071 and p120-catenin. The degradation of these proteins is achieved by co-opting the lysosomal and the ubiquitin proteasome system of the host cell. The degradation of p0071 and p120-catenin induced the decreased E-cadherin membrane localization, thus, this strategy may allow L. interrogans to disassemble AJCs
and disseminate through the body efficiently.

Free Research Field

病原細菌学

Academic Significance and Societal Importance of the Research Achievements

本研究でレプトスピラは宿主真核細胞のタンパク質分解系をハイジャックすることによって、p0071とp120-カテニンを分解し、細胞間接着装置が破壊されることを明らかにした。本研究で得られた新規知見は、レプトスピラ症の病態形成メカニズムの理解に寄与し、本感染症を制御するためには、複数の経路が抑制可能であることがわかった。
レプトスピラがどのように宿主真核細胞のタンパク質分解系を利用するかを明らかになることによって、必須細菌因子や細胞内伝達経路を阻止し、レプトスピラ症を制御できる新たな治療法の開発が期待できる。