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A whole-cell platform for discovering synthetic cell adhesion molecules in bacteria

Author

Listed:
  • Po-Yin Chen

    (Academia Sinica
    Academia Sinica and National Defense Medical Center)

  • Yung-Chih Chen

    (Academia Sinica)

  • Po-Pang Chen

    (Academia Sinica
    National Yang Ming Chiao Tung University)

  • Kuan-Ting Lin

    (Academia Sinica
    National Yang-Ming Chao-Tung University and Academia Sinica)

  • Karen Sargsyan

    (Academia Sinica)

  • Chao-Ping Hsu

    (Academia Sinica
    National Center for Theoretical Sciences
    National Taiwan University)

  • Wei-Le Wang

    (Academia Sinica
    Academia Sinica and National Defense Medical Center
    National Yang-Ming Chao-Tung University and Academia Sinica)

  • Kuo-Chiang Hsia

    (Academia Sinica
    Academia Sinica and National Defense Medical Center
    National Yang Ming Chiao Tung University)

  • See-Yeun Ting

    (Academia Sinica
    Academia Sinica and National Defense Medical Center
    National Taiwan University)

Abstract

Developing programmable bacterial cell-cell adhesion is of significant interest due to its versatile applications. Current methods that rely on presenting cell adhesion molecules (CAMs) on bacterial surfaces are limited by the lack of a generalizable strategy to identify such molecules targeting bacterial membrane proteins in their natural states. Here, we introduce a whole-cell screening platform designed to discover CAMs targeting bacterial membrane proteins within a synthetic bacteria-displayed nanobody library. Leveraging the potency of the bacterial type IV secretion system—a contact-dependent DNA delivery nanomachine—we have established a positive feedback mechanism to selectively enrich for bacteria displaying nanobodies that target antigen-expressing cells. Our platform successfully identified functional CAMs capable of recognizing three distinct outer membrane proteins (TraN, OmpA, OmpC), demonstrating its efficacy in CAM discovery. This approach holds promise for engineering bacterial cell-cell adhesion, such as directing the antibacterial activity of programmed inhibitor cells toward target bacteria in mixed populations.

Suggested Citation

  • Po-Yin Chen & Yung-Chih Chen & Po-Pang Chen & Kuan-Ting Lin & Karen Sargsyan & Chao-Ping Hsu & Wei-Le Wang & Kuo-Chiang Hsia & See-Yeun Ting, 2024. "A whole-cell platform for discovering synthetic cell adhesion molecules in bacteria," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
  • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-51017-1
    DOI: 10.1038/s41467-024-51017-1
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    References listed on IDEAS

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    1. Peter Eastman & Jason Swails & John D Chodera & Robert T McGibbon & Yutong Zhao & Kyle A Beauchamp & Lee-Ping Wang & Andrew C Simmonett & Matthew P Harrigan & Chaya D Stern & Rafal P Wiewiora & Bernar, 2017. "OpenMM 7: Rapid development of high performance algorithms for molecular dynamics," PLOS Computational Biology, Public Library of Science, vol. 13(7), pages 1-17, July.
    2. Honesty Kim & Dominic J. Skinner & David S. Glass & Alexander E. Hamby & Bradey A. R. Stuart & Jörn Dunkel & Ingmar H. Riedel-Kruse, 2022. "4-bit adhesion logic enables universal multicellular interface patterning," Nature, Nature, vol. 608(7922), pages 324-329, August.
    3. Alistair B. Russell & Michele LeRoux & Krisztina Hathazi & Danielle M. Agnello & Takahiko Ishikawa & Paul A. Wiggins & Sun Nyunt Wai & Joseph D. Mougous, 2013. "Diverse type VI secretion phospholipases are functionally plastic antibacterial effectors," Nature, Nature, vol. 496(7446), pages 508-512, April.
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