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Composition and liquid-to-solid maturation of protein aggregates contribute to bacterial dormancy development and recovery

Author

Listed:
  • Celien Bollen

    (KU Leuven
    VIB-KU Leuven)

  • Sofie Louwagie

    (KU Leuven
    VIB-KU Leuven)

  • Femke Deroover

    (KU Leuven
    VIB-KU Leuven)

  • Wouter Duverger

    (VIB-KU Leuven
    KU Leuven)

  • Ladan Khodaparast

    (VIB-KU Leuven
    KU Leuven)

  • Laleh Khodaparast

    (VIB-KU Leuven
    KU Leuven)

  • Dieter Hofkens

    (KU Leuven
    VIB-KU Leuven)

  • Joost Schymkowitz

    (VIB-KU Leuven
    KU Leuven)

  • Frederic Rousseau

    (VIB-KU Leuven
    KU Leuven)

  • Liselot Dewachter

    (KU Leuven
    VIB-KU Leuven
    Université catholique de Louvain)

  • Jan Michiels

    (KU Leuven
    VIB-KU Leuven)

Abstract

Recalcitrant bacterial infections can be caused by various types of dormant bacteria, including persisters and viable but nonculturable (VBNC) cells. Despite their clinical importance, we know fairly little about bacterial dormancy development and recovery. Previously, we established a correlation between protein aggregation and dormancy in Escherichia coli. Here, we present further support for a direct relationship between both. Our experiments demonstrate that aggregates progressively sequester proteins involved in energy production, thereby likely causing ATP depletion and dormancy. Furthermore, we demonstrate that structural features of protein aggregates determine the cell’s ability to exit dormancy and resume growth. Proteins were shown to first assemble in liquid-like condensates that solidify over time. This liquid-to-solid phase transition impedes aggregate dissolution, thereby preventing growth resumption. Our data support a model in which aggregate structure, rather than cellular activity, marks the transition from the persister to the VBNC state.

Suggested Citation

  • Celien Bollen & Sofie Louwagie & Femke Deroover & Wouter Duverger & Ladan Khodaparast & Laleh Khodaparast & Dieter Hofkens & Joost Schymkowitz & Frederic Rousseau & Liselot Dewachter & Jan Michiels, 2025. "Composition and liquid-to-solid maturation of protein aggregates contribute to bacterial dormancy development and recovery," Nature Communications, Nature, vol. 16(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-56387-8
    DOI: 10.1038/s41467-025-56387-8
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    References listed on IDEAS

    as
    1. Mehmet A. Orman & Mark P. Brynildsen, 2015. "Inhibition of stationary phase respiration impairs persister formation in E. coli," Nature Communications, Nature, vol. 6(1), pages 1-13, November.
    2. Ladan Khodaparast & Laleh Khodaparast & Rodrigo Gallardo & Nikolaos N. Louros & Emiel Michiels & Reshmi Ramakrishnan & Meine Ramakers & Filip Claes & Lydia Young & Mohammad Shahrooei & Hannah Wilkinso, 2018. "Aggregating sequences that occur in many proteins constitute weak spots of bacterial proteostasis," Nature Communications, Nature, vol. 9(1), pages 1-15, December.
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