Incoherent feedback from coupled amino acids and ribosome pools generates damped oscillations in growing E. coli
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.
Authors
- Luca Ciandrini (ORCID: https://orcid.org/0000-0001-5859-2764)
- Jacopo Grilli (ORCID: https://orcid.org/0000-0002-8235-5803)
- Bianca Sclavi (ORCID: https://orcid.org/0000-0002-3883-8592)
- Ilaria Iuliani (ORCID: https://orcid.org/0000-0003-1758-0497)
- Marco Cosentino Lagomarsino (ORCID: https://orcid.org/0000-0003-0235-0445)
- Rossana Droghetti (ORCID: https://orcid.org/0000-0002-4596-7288)
- Giorgio Tallarico (ORCID: https://orcid.org/0000-0002-3925-9699)
- Valerio Firmano
- Ludovico Calabrese (ORCID: https://orcid.org/0000-0002-1305-4441)
- Pinhas Fuchs (ORCID: https://orcid.org/0000-0002-6280-8369)
Institutions
- The Abdus Salam International Centre for Theoretical Physics (ICTP) (IT)
- SIB Swiss Institute of Bioinformatics (CH)
- Centre National de la Recherche Scientifique (FR)
- Inserm (FR)
- University of Basel (CH)
- Institut Universitaire de France (FR)
- University of Milan (IT)
- Université de Montpellier (FR)
- Pázmány Péter Catholic University (HU)
- Sorbonne Université (FR)
- Biologie Computationnelle, Quantitative et Synthétique (FR)
- Centre de Biologie Structurale (FR)
- IFOM (IT)
- Istituto Nazionale di Fisica Nucleare, Sezione di Milano (IT)
- University of Lausanne (CH)
Publication Details
- Journal
- Nature Communications
- Published
- 2025-03-29
- DOI
- https://doi.org/10.1038/s41467-025-57789-4
- Citations
- 5
- Primary Topic
- Microbial Metabolic Engineering and Bioproduction
- Type
- article
- Field-Weighted Citation Impact
- 4.03
Funders
- Agence Nationale de la Recherche
- Associazione Italiana per la Ricerca sul Cancro