Incoherent feedback from coupled amino acids and ribosome pools generates damped oscillations in growing E. coli

Rossana Droghetti (), Philippe Fuchs, Ilaria Iuliani, Valerio Firmano, Giorgio Tallarico, Ludovico Calabrese, Jacopo Grilli, Bianca Sclavi, Luca Ciandrini and Marco Cosentino Lagomarsino ()
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Rossana Droghetti: IFOM - Istituto Fondazione di Oncologia Molecolare
Philippe Fuchs: Universitè de Montpellier, CNRS, INSERM
Ilaria Iuliani: CNRS, Laboratory of Computational, Quantitative and Synthetic Biology, CQSB
Valerio Firmano: Università degli Studi di Milano
Giorgio Tallarico: IFOM - Istituto Fondazione di Oncologia Molecolare
Ludovico Calabrese: IFOM - Istituto Fondazione di Oncologia Molecolare
Jacopo Grilli: The Abdus Salam International Center for Theoretical Physics
Bianca Sclavi: CNRS, Laboratory of Computational, Quantitative and Synthetic Biology, CQSB
Luca Ciandrini: Universitè de Montpellier, CNRS, INSERM
Marco Cosentino Lagomarsino: IFOM - Istituto Fondazione di Oncologia Molecolare

Nature Communications, 2025, vol. 16, issue 1, 1-12

Abstract: Abstract Current theories of bacterial growth physiology demonstrate impressive predictive power but are often phenomenological, lacking mechanistic detail. Incorporating such details would significantly enhance our ability to predict and control bacterial growth under varying environmental conditions. The “Flux Controlled Regulation” (FCR) model serves as a reference framework, linking ribosome allocation to translation efficiency through a steady-state assumption. However, it neglects ppGpp-mediated nutrient sensing and transcriptional regulation of ribosomal operons. Here, we propose a mechanistic model that extends the FCR framework by incorporating three key components: (i) the amino acid pool, (ii) ppGpp sensing of translation elongation rate, and (iii) transcriptional regulation of protein allocation by ppGpp-sensitive promoters. Our model aligns with observed steady-state growth laws and makes testable predictions for unobserved quantities. We show that during environmental changes, the incoherent feedback between sensing and regulation generates oscillatory relaxation dynamics, a behavior that we support by new and existing experimental data.

Date: 2025
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DOI: 10.1038/s41467-025-57789-4

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