An international research team led by scientists from Humboldt-Universit?t zu Berlin (HU) has decoded the complete structure of the bacterial flagellum. The findings provide important insights into the molecular structure of one of nature's most complex locomotor systems. "Our study solves a central puzzle in microbiology that has occupied researchers since the 1950s: How does the cell manage to build this huge molecular machine so precisely and efficiently outside its cell body?" says Prof Marc Erhardt, head of the Molecular Microbiology research group at Humboldt-Universit?t zu Berlin and last author of the study. The flagellum could be visualised in its native state, i.e. in the active, correctly folded form of the molecule. In addition, the team succeeded in elucidating previously unknown key moments of biological self-assembly. Through this process, the complex structures of the flagellum are assembled step by step in the bacterium. The results of the research were published in the journal Nature Microbiology. Scientists from the Randall Centre for Cell and Molecular Biophysics, King's College London, Forschungszentrum Jülich, Imperial College London and the Max Planck Research Centre for the Science of Pathogens in Berlin are involved in the study.
The bacterial flagella
The bacterial flagella is one of the largest and most complex macromolecular machines in nature. It consists of a basal body, a hook and a long extracellular filament, a long, thin protein thread. By rotating the flagellum, pathogenic microorganisms such as Salmonella enterica and Campylobacter jejuni can move around, adhere to surfaces and colonise host cells. Despite decades of research, it was previously unclear how the flagellum, which is several micrometres long, is constructed on the cell surface and how new building blocks, so-called flagellins, are incorporated into the growing filament.
"The bacterial flagellum is a prime example of molecular precision and efficiency. Our study reveals its architecture in unprecedented detail and creates a basis for future work on bacterial motility, infection and synthetic biology," says Prof. Marc Erhardt, whose research focuses on the mechanisms of bacterial locomotion and phage defence systems.
Far-reaching significance for microbiology and biotechnology
The results not only provide a complete structural model of bacterial flagella, but also clarify fundamental principles of the self-assembly of macromolecular complexes. In the long term, the findings could contribute to the development of new antimicrobial strategies or the construction of synthetic nanomachines.
A look into the molecular engine room
Using state-of-the-art cryo-electron microscopy, the scientists were able to image the complete extracellular flagella of Salmonella with almost atomic resolution. For the first time, they were able to visualise the natural structure of the filament cap, a small protein at the tip of the flagella, in various phases of its assembly as a functional five-complex. They were also able to visualise the previously unknown structure of the connection between the hook and the filament. The flagellum of Campylobacter was also analysed in a very early structural state, before the actual filament structure begins. Through targeted genetic modifications and functional tests, the scientists were able to show that the filament cap must rotate and flexibly adapt its shape so that new building blocks of the filament (the flagellin molecules) can be incorporated one after the other and folded correctly. The connection between the hook and the filament acts like a buffer: it absorbs mechanical stresses and at the same time ensures that the individual components are assembled correctly.
"It was a unique experience to capture snapshots of a molecular construction process that had previously been in the dark," says Rosa Einenkel, first author of the study and doctoral student at Humboldt-Universit?t zu Berlin. She is focussing on the function and structure of the bacterial flagellum. "Seeing how individual flagellin molecules are precisely folded and inserted into the growing filament was like deciphering a molecular ballet."
Further information
Publication
Rosa Einenkel, Kailin Qin, Julia Schmidt, Natalie S. Al-Otaibi, Daniel Mann, Tina Drobni?, Eli J. Cohen, Nayim Gonzalez-Rodriguez, Jane Harrowell, Elena Shmakova, Morgan Beeby, Marc Erhardt, Julien R. C. Bergeron. The structure of the complete extracellular bacterial flagellum reveals the mechanism of flagellin incorporation.Nature Microbiology (2025) s41564-025-02037-0
Image of the bacterial flagellum
Contact Prof. Dr. Marc Erhardt
Prof Dr Marc Erhardt
Department of Biology, Humboldt-Universit?t zu Berlin
Molecular Microbiology Research Group
Phone: 030 2093-49780
X: x.com/Salmo_lab
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Rosa Einenkel
Department of Biology, Humboldt-Universit?t zu Berlin
Molecular Microbiology Research Group
Phone: 030 2093-49693
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Dr Julien C. Bergeron
Randall Centre for Cell and Molecular Biophysics, Kings' College London
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