IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v15y2024i1d10.1038_s41467-024-51017-1.html
   My bibliography  Save this article

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
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-024-51017-1
    File Function: Abstract
    Download Restriction: no

    File URL: https://libkey.io/10.1038/s41467-024-51017-1?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    1. 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.
    2. 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.
    3. 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.
    Full references (including those not matched with items on IDEAS)

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Christian Hentrich & Mateusz Putyrski & Hanh Hanuschka & Waldemar Preis & Sarah-Jane Kellmann & Melissa Wich & Manuel Cavada & Sarah Hanselka & Victor S. Lelyveld & Francisco Ylera, 2024. "Engineered reversible inhibition of SpyCatcher reactivity enables rapid generation of bispecific antibodies," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    2. Andreas Mardt & Tim Hempel & Cecilia Clementi & Frank Noé, 2022. "Deep learning to decompose macromolecules into independent Markovian domains," Nature Communications, Nature, vol. 13(1), pages 1-11, December.
    3. Cheng Shen & Yuqing Zhang & Wenwen Cui & Yimeng Zhao & Danqi Sheng & Xinyu Teng & Miaoqing Shao & Muneyoshi Ichikawa & Jin Wang & Motoyuki Hattori, 2023. "Structural insights into the allosteric inhibition of P2X4 receptors," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    4. F. P. Panei & P. Gkeka & M. Bonomi, 2024. "Identifying small-molecules binding sites in RNA conformational ensembles with SHAMAN," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    5. Shana Bergman & Rosemary J. Cater & Ambrose Plante & Filippo Mancia & George Khelashvili, 2023. "Substrate binding-induced conformational transitions in the omega-3 fatty acid transporter MFSD2A," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    6. Kuang-Ting Ko & Frank Lennartz & David Mekhaiel & Bora Guloglu & Arianna Marini & Danielle J. Deuker & Carole A. Long & Matthijs M. Jore & Kazutoyo Miura & Sumi Biswas & Matthew K. Higgins, 2022. "Structure of the malaria vaccine candidate Pfs48/45 and its recognition by transmission blocking antibodies," Nature Communications, Nature, vol. 13(1), pages 1-11, December.
    7. Hongjun Bai & Eric Lewitus & Yifan Li & Paul V. Thomas & Michelle Zemil & Mélanie Merbah & Caroline E. Peterson & Thujitha Thuraisamy & Phyllis A. Rees & Agnes Hajduczki & Vincent Dussupt & Bonnie Sli, 2024. "Contemporary HIV-1 consensus Env with AI-assisted redesigned hypervariable loops promote antibody binding," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    8. Do Hoon Kwon & Feng Zhang & Brett A. McCray & Shasha Feng & Meha Kumar & Jeremy M. Sullivan & Wonpil Im & Charlotte J. Sumner & Seok-Yong Lee, 2023. "TRPV4-Rho GTPase complex structures reveal mechanisms of gating and disease," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    9. Ritaban Halder & Daniel A. Nissley & Ian Sitarik & Yang Jiang & Yiyun Rao & Quyen V. Vu & Mai Suan Li & Justin Pritchard & Edward P. O’Brien, 2023. "How soluble misfolded proteins bypass chaperones at the molecular level," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    10. Giacomo Janson & Gilberto Valdes-Garcia & Lim Heo & Michael Feig, 2023. "Direct generation of protein conformational ensembles via machine learning," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    11. Jeffrey A. Ruffolo & Lee-Shin Chu & Sai Pooja Mahajan & Jeffrey J. Gray, 2023. "Fast, accurate antibody structure prediction from deep learning on massive set of natural antibodies," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    12. Jin H. Yang & Hugo B. Brandão & Anders S. Hansen, 2023. "DNA double-strand break end synapsis by DNA loop extrusion," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    13. Rodrigo G. Fernandez Lahore & Niccolò P. Pampaloni & Enrico Schiewer & M.-Marcel Heim & Linda Tillert & Johannes Vierock & Johannes Oppermann & Jakob Walther & Dietmar Schmitz & David Owald & Andrew J, 2022. "Calcium-permeable channelrhodopsins for the photocontrol of calcium signalling," Nature Communications, Nature, vol. 13(1), pages 1-18, December.
    14. Yi-Tzu Kuo & Amanda Souza Câmara & Veit Schubert & Pavel Neumann & Jiří Macas & Michael Melzer & Jianyong Chen & Jörg Fuchs & Simone Abel & Evelyn Klocke & Bruno Huettel & Axel Himmelbach & Dmitri Dem, 2023. "Holocentromeres can consist of merely a few megabase-sized satellite arrays," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    15. S. M. Ayala Mariscal & M. L. Pigazzini & Y. Richter & M. Özel & I. L. Grothaus & J. Protze & K. Ziege & M. Kulke & M. ElBediwi & J. V. Vermaas & L. Colombi Ciacchi & S. Köppen & F. Liu & J. Kirstein, 2022. "Identification of a HTT-specific binding motif in DNAJB1 essential for suppression and disaggregation of HTT," Nature Communications, Nature, vol. 13(1), pages 1-25, December.
    16. Nicolas Papadopoulos & Audrey Nédélec & Allison Derenne & Teodor Asvadur Şulea & Christian Pecquet & Ilyas Chachoua & Gaëlle Vertenoeil & Thomas Tilmant & Andrei-Jose Petrescu & Gabriel Mazzucchelli &, 2023. "Oncogenic CALR mutant C-terminus mediates dual binding to the thrombopoietin receptor triggering complex dimerization and activation," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    17. Janni Harju & Muriel C. F. Teeseling & Chase P. Broedersz, 2024. "Loop-extruders alter bacterial chromosome topology to direct entropic forces for segregation," Nature Communications, Nature, vol. 15(1), pages 1-10, December.
    18. Tom Dixon & Derek MacPherson & Barmak Mostofian & Taras Dauzhenka & Samuel Lotz & Dwight McGee & Sharon Shechter & Utsab R. Shrestha & Rafal Wiewiora & Zachary A. McDargh & Fen Pei & Rajat Pal & João , 2022. "Predicting the structural basis of targeted protein degradation by integrating molecular dynamics simulations with structural mass spectrometry," Nature Communications, Nature, vol. 13(1), pages 1-24, December.
    19. Joseph G. Beton & Thomas Mulvaney & Tristan Cragnolini & Maya Topf, 2024. "Cryo-EM structure and B-factor refinement with ensemble representation," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
    20. Re’em Moskovitz & Tossapol Pholcharee & Sophia M. DonVito & Bora Guloglu & Edward Lowe & Franziska Mohring & Robert W. Moon & Matthew K. Higgins, 2023. "Structural basis for DARC binding in reticulocyte invasion by Plasmodium vivax," Nature Communications, Nature, vol. 14(1), pages 1-9, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-51017-1. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.