Milestone in Understanding Bacterial Motility

Researchers solve the mystery of how bacteria build their motility machinery

So sieht die Struktur einer Bakterien-Gei?el aus: Der lange Faden, das sogenannte Filament (rosa). Die Kappe (orange), die hilft, den Faden zusammenzubauen. Weitere Teile sind der Haken (blau) und die Verbindung zwischen Haken und Faden (gelb und grün). Bild: Prof. Marc Erhardt

This is what the structure of
a bacterial flagellum looks like:
the long thread, called the
filament (pink); the cap (orange),
which helps assemble the thread;
other components include the
hook (blue) and the junction
between hook and filament
(yellow and green).
Photo: Prof. Marc Erhardt

An international research team led by scientists at Humboldt-Universit?t zu Berlin (HU) has resolved the complete structure of the bacterial flagellum. These findings provide key insights into the molecular architecture of one of the most complex motility machines in nature. “Our study solves a central mystery in microbiology that has intrigued researchers since the 1950s: how does the cell manage to assemble this sophisticated molecular machine so precisely and efficiently outside of its body?” says Prof. Marc Erhardt, head of the Molecular Microbiology group at Humboldt-Universit?t zu Berlin and senior author of the study. The flagellum was imaged in its native state, its active, properly folded molecular form. The team also succeeded in elucidating previously unknown key moments in the biological self-assembly process by which the flagellum is built step by step on the bacterial surface. The findings were published in the journal Nature Microbiology. The study involved scientists from the Randall Centre for Cell and Molecular Biophysics at King’s College London, Forschungszentrum Jülich, Imperial College London, and the Max Planck Unit for the Science of Pathogens in Berlin.

The Bacterial Flagellum

The bacterial flagellum is one of the largest and most complex macromolecular machines found in nature. It consists of a basal body, a hook, and a long extracellular filament, a thin protein filament. By rotating the flagellum, pathogenic microorganisms such as Salmonella enterica and Campylobacter jejuni can move in a directed manner, adhere to surfaces, and colonize host cells. Despite decades of research, it remained unclear how the several-micrometer-long flagellum is assembled on the cell surface, and how new subunits, known as 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 lays the groundwork for future research on bacterial motility, infection, and synthetic biology,” says Prof. Marc Erhardt, whose research focuses on mechanisms of bacterial motility and phage defense systems.

Broad Relevance for Microbiology and Biotechnology

The results not only provide a complete structural model of the bacterial flagellum but also clarify fundamental principles of how large macromolecular complexes can self-assemble. These insights could, in the long term, aid in the development of novel antimicrobial strategies or the design of synthetic nanomachines.

A Glimpse into the Molecular Engine Room

Using cutting-edge cryo-electron microscopy, the researchers were able to visualize the complete extracellular flagellum of Salmonella at near-atomic resolution. For the first time, they captured the natural structure of the filament cap, a small protein at the tip of the flagellum, at multiple stages of assembly as a functional pentameric complex. They also resolved the previously unknown structure of the junction between the hook and the filament. The Campylobacter flagellum was imaged in a very early assembly state, before filament elongation begins. Through targeted genetic mutations and functional assays, the researchers demonstrated that the filament cap must rotate and flexibly adapt its shape to allow new filament subunits (flagellin molecules) to be sequentially inserted and correctly folded. The hook-filament junction acts as a buffer: it absorbs mechanical stress while ensuring the precise positioning of each structural component.

“It was a unique experience to capture snapshots of a molecular assembly process that had remained hidden until now,” says Rosa Einenkel, first author of the study and a doctoral researcher at Humboldt-Universit?t zu Berlin, who studies the structure and function of the bacterial flagellum. “Watching individual flagellin molecules fold precisely and insert into the growing filament felt like deciphering a molecular ballet.”

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.