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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
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    References listed on IDEAS

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    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.
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    Cited by:

    1. Jung Hun Park & Gábor Holló & Yolanda Schaerli, 2024. "From resonance to chaos by modulating spatiotemporal patterns through a synthetic optogenetic oscillator," Nature Communications, Nature, vol. 15(1), pages 1-13, December.

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