Bacterial motility depends on a critical flagellum length and energy-optimized assembly
The flagellum is the most complex macromolecular structure known in bacteria and is composed of around two dozen distinct proteins. The main building block of the long, external flagellar filament, flagellin, is secreted through the flagellar type-III secretion system at a remarkable rate of several tens of thousands of amino acids per second, significantly surpassing the rates achieved by other pore-based protein secretion systems. The evolutionary implications and potential benefits of this high secretion rate for flagellum assembly and function, however, have remained elusive. In this study, we provide both experimental and theoretical evidence that the flagellar secretion rate has been evolutionarily optimized to facilitate rapid and efficient construction of a functional flagellum. By synchronizing flagellar assembly, we found that a minimal filament length of 2.5 μm was required for swimming motility. Biophysical modeling revealed that this minimal filament length threshold resulted from an elasto-hydrodynamic instability of the whole swimming cell, dependent on the filament length. Furthermore, we developed a stepwise filament labeling method combined with electron microscopy visualization to validate predicted flagellin secretion rates of up to 10,000 amino acids per second. A biophysical model of flagellum growth demonstrates that the observed high flagellin secretion rate efficiently balances filament elongation and energy consumption, thereby enabling motility in the shortest amount of time. Taken together, these insights underscore the evolutionary pressures that have shaped the development and optimization of the flagellum and type-III secretion system, illuminating the intricate interplay and cost-benefit tradeoff between functionality and efficiency in assembly of large macromolecular structures.
Authors
- Eric Lauga (ORCID: https://orcid.org/0000-0002-8916-2545)
- Adrien Ducret (ORCID: https://orcid.org/0000-0002-9076-405X)
- Svenja Fischer (ORCID: https://orcid.org/0000-0003-1297-3312)
- Philipp F. Popp (ORCID: https://orcid.org/0000-0002-7825-1550)
- Christian Goosmann
- David Hathcock (ORCID: https://orcid.org/0000-0003-4551-9239)
- Thibaud T. Renault (ORCID: https://orcid.org/0000-0002-1530-2613)
- Emmanuelle Charpentier (ORCID: https://orcid.org/0000-0002-0254-0778)
- Manuel Halte (ORCID: https://orcid.org/0000-0001-9876-7493)
- Marc Erhardt (ORCID: https://orcid.org/0000-0001-6292-619X)
- John Severn (ORCID: https://orcid.org/0009-0001-2098-4997)
- Yuhai Tu (ORCID: https://orcid.org/0000-0002-4589-981X)
Institutions
- Université de Bordeaux (FR)
- Inserm (FR)
- Université de Lyon (FR)
- University of Cambridge (GB)
- Humboldt-Universität zu Berlin (DE)
- Max Planck Institute for Infection Biology (DE)
- Institut de Biologie et de Chimie des Protéines (FR)
- Régulations Naturelle et Artificielle (FR)
- IBM Research - Thomas J. Watson Research Center (US)
- Environnement, ville, société (FR)
- Max Planck Unit for the Science of Pathogens (DE)
- Acides nucléiques: Régulations naturelles et artificielles (FR)
Publication Details
- Journal
- Proceedings of the National Academy of Sciences
- Published
- 2025-03-11
- DOI
- https://doi.org/10.1073/pnas.2413488122
- Citations
- 6
- Primary Topic
- Lipid Membrane Structure and Behavior
- Type
- article
- Field-Weighted Citation Impact
- 4.84
Funders
- Alexander von Humboldt-Stiftung
- Agence Nationale de la Recherche
- National Institute of General Medical Sciences
- HORIZON EUROPE European Research Council