IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v14y2023i1d10.1038_s41467-023-43241-y.html
   My bibliography  Save this article

Synthetic genetic oscillators demonstrate the functional importance of phenotypic variation in pneumococcal-host interactions

Author

Listed:
  • Anne-Stéphanie Rueff

    (University of Lausanne, Biophore Building)

  • Renske Raaphorst

    (University of Lausanne, Biophore Building
    de Duve Institute, UCLouvain)

  • Surya D. Aggarwal

    (New York University School of Medicine)

  • Javier Santos-Moreno

    (University of Lausanne, Biophore Building
    Pompeu Fabra University)

  • Géraldine Laloux

    (de Duve Institute, UCLouvain)

  • Yolanda Schaerli

    (University of Lausanne, Biophore Building)

  • Jeffrey N. Weiser

    (New York University School of Medicine)

  • Jan-Willem Veening

    (University of Lausanne, Biophore Building
    University of California San Diego
    University of California San Diego)

Abstract

Phenotypic variation is the phenomenon in which clonal cells display different traits even under identical environmental conditions. This plasticity is thought to be important for processes including bacterial virulence, but direct evidence for its relevance is often lacking. For instance, variation in capsule production in the human pathogen Streptococcus pneumoniae has been linked to different clinical outcomes, but the exact relationship between variation and pathogenesis is not well understood due to complex natural regulation. In this study, we use synthetic oscillatory gene regulatory networks (GRNs) based on CRISPR interference (CRISPRi) together with live cell imaging and cell tracking within microfluidics devices to mimic and test the biological function of bacterial phenotypic variation. We provide a universally applicable approach for engineering intricate GRNs using only two components: dCas9 and extended sgRNAs (ext-sgRNAs). Our findings demonstrate that variation in capsule production is beneficial for pneumococcal fitness in traits associated with pathogenesis providing conclusive evidence for this longstanding question.

Suggested Citation

  • Anne-Stéphanie Rueff & Renske Raaphorst & Surya D. Aggarwal & Javier Santos-Moreno & Géraldine Laloux & Yolanda Schaerli & Jeffrey N. Weiser & Jan-Willem Veening, 2023. "Synthetic genetic oscillators demonstrate the functional importance of phenotypic variation in pneumococcal-host interactions," Nature Communications, Nature, vol. 14(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-43241-y
    DOI: 10.1038/s41467-023-43241-y
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-023-43241-y
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-023-43241-y?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. Martin Ackermann & Bärbel Stecher & Nikki E. Freed & Pascal Songhet & Wolf-Dietrich Hardt & Michael Doebeli, 2008. "Self-destructive cooperation mediated by phenotypic noise," Nature, Nature, vol. 454(7207), pages 987-990, August.
    2. Médéric Diard & Victor Garcia & Lisa Maier & Mitja N. P. Remus-Emsermann & Roland R. Regoes & Martin Ackermann & Wolf-Dietrich Hardt, 2013. "Stabilization of cooperative virulence by the expression of an avirulent phenotype," Nature, Nature, vol. 494(7437), pages 353-356, February.
    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. Peña, Jorge & Cooper, Guy Alexander & Liu, Ming & West, Stuart Andrew, 2020. "Dividing labour in social microorganisms: coordinated or random specialisation?," IAST Working Papers 20-104, Institute for Advanced Study in Toulouse (IAST).
    2. Te Wu & Long Wang & Feng Fu, 2017. "Coevolutionary dynamics of phenotypic diversity and contingent cooperation," PLOS Computational Biology, Public Library of Science, vol. 13(1), pages 1-16, January.
    3. Manalee Vishnu Surve & Smita Bhutda & Akshay Datey & Anjali Anil & Shalini Rawat & Athira Pushpakaran & Dipty Singh & Kwang Sik Kim & Dipshikha Chakravortty & Anirban Banerjee, 2018. "Heterogeneity in pneumolysin expression governs the fate of Streptococcus pneumoniae during blood-brain barrier trafficking," PLOS Pathogens, Public Library of Science, vol. 14(7), pages 1-29, July.
    4. Felix J H Hol & Peter Galajda & Krisztina Nagy & Rutger G Woolthuis & Cees Dekker & Juan E Keymer, 2013. "Spatial Structure Facilitates Cooperation in a Social Dilemma: Empirical Evidence from a Bacterial Community," PLOS ONE, Public Library of Science, vol. 8(10), pages 1-10, October.
    5. Peña, Jorge & Nöldeke, Georg & Lehmann, Laurent, 2014. "Relatedness and synergies of kind and scale in the evolution of helping," Working papers 2014/09, Faculty of Business and Economics - University of Basel.
    6. Eran Even-Tov & Shira Omer Bendori & Julie Valastyan & Xiaobo Ke & Shaul Pollak & Tasneem Bareia & Ishay Ben-Zion & Bonnie L Bassler & Avigdor Eldar, 2016. "Social Evolution Selects for Redundancy in Bacterial Quorum Sensing," PLOS Biology, Public Library of Science, vol. 14(2), pages 1-18, February.
    7. Jan J. Kreider & Thijs Janzen & Abel Bernadou & Daniel Elsner & Boris H. Kramer & Franz J. Weissing, 2022. "Resource sharing is sufficient for the emergence of division of labour," Nature Communications, Nature, vol. 13(1), pages 1-9, December.
    8. Karl P. Gerhardt & Satyajit D. Rao & Evan J. Olson & Oleg A. Igoshin & Jeffrey J. Tabor, 2021. "Independent control of mean and noise by convolution of gene expression distributions," Nature Communications, Nature, vol. 12(1), pages 1-10, December.
    9. Si Tang & Yaqing Liu & Jianming Zhu & Xueyu Cheng & Lu Liu & Katrin Hammerschmidt & Jin Zhou & Zhonghua Cai, 2024. "Bet hedging in a unicellular microalga," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
    10. Czuppon, Peter & Gokhale, Chaitanya S., 2018. "Disentangling eco-evolutionary effects on trait fixation," Theoretical Population Biology, Elsevier, vol. 124(C), pages 93-107.
    11. Patrick Kaiser & Emma Slack & Andrew J Grant & Wolf-Dietrich Hardt & Roland R Regoes, 2013. "Lymph Node Colonization Dynamics after Oral Salmonella Typhimurium Infection in Mice," PLOS Pathogens, Public Library of Science, vol. 9(9), pages 1-12, September.

    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:14:y:2023:i:1:d:10.1038_s41467-023-43241-y. 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.