Towards a new type of antibiotic: elucidation of the activation signal and signal transduction mechanism of the type III secretion system of Shigella flexneri

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K16661
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 49050:Bacteriology-related
• Research Institution: Okinawa Institute of Science and Technology Graduate University
• Principal Investigator: Cheung Martin 沖縄科学技術大学院大学, 量子波光学顕微鏡ユニット, 技術員 (90832163)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: Shigella flexneri / Type III secretion / Tip complex / Cryo-EM

Outline of Final Research Achievements

Utilizing cryo-EM and mass spectrometry to study the type III secretion system tip complex (TC), two key findings were made: i) the TC comprises three distinct subunits with heterogeneous morphologies. Prior to this study, the TC had never been visualized to better than 20 A resolution and was believed to be a homopentameric complex. By visualizing, for the first time, the TC to sub-nanometer resolution (app. 9 A) by cryo-EM, this work revealed the TC to be a trimeric complex. Furthermore, each subunit within the trimer assumes a distinct orientation; ii) a hitherto unknown auxiliary complex binds to the TC upon activation of the T3SS during infection. A pore contiguous with the TC is known to be inserted into target cell membranes during infection. We believe this newly identified complex to be a pre-pore complex and may explain how the TC is able to interact with target cells.

Free Research Field

Microbiology

Academic Significance and Societal Importance of the Research Achievements

These results could be highly significant not only for our fundamental understanding of type III secretion system function but also for the development of novel antimicrobials. The newly complex may serve as an ideal drug target to prevent the infectivity of Shigella.