Protein cogwheel gives flagellum two directions of rotation

Many bacterial species have one or more flagella. Thanks to these long whip-like tails that rotate around their axis, bacteria can move and search for nutrients in their environment or find a host to infect. The flagellum can rapidly change its direction of rotation, and this determines the course of the bacterium. How exactly this switching works has been the subject of research for years.

Flagella are a fine example of bio-nanotechnology, as each flagellum is attached to a rotor: a ring-shaped, rotating protein complex with dozens of sub-units. This allows the bacterial cell to convert the flow of protons through motor proteins into rotation either clockwise or anticlockwise. The question is precisely how the rotor changes direction.

Two papers have recently appeared in Nature Microbiology that provide a clearer picture. Both a team led by British researcher Susan Lea and one led by American researcher Tina Iverson zoom in on the switching mechanism using an electron microscope. They demonstrate how a small conformational change in a protein determines the direction of rotation.

Cogs

‘I think the main conclusions of both papers are very similar,’ says Ariane Briegel, Professor of Electron Cryo-Tomography and Bacterial Chemotaxis at Leiden University. ‘Lea’s paper examines the entire protein complex, while Iverson’s paper analyses a smaller component. But both yield roughly the same model of how the switching might work.’

Broadly speaking, Lea and Iverson describe a system with two cogs. The ring of the flagellar rotor can be thought of as a large cog driven by a smaller one: the motor protein (MotA/B). The shape of the large cog determines where the motor proteins make contact. If the motor protein engages on the outside, the rotor turns anticlockwise; if it engages on the inside, the rotor turns clockwise. In an animation on YouTube (see below), Lea’s group shows how this switching takes place: the motor protein is shown in colour, the flagellar rotor in grey.

Whether this description based on microscopy is one hundred per cent correct remains uncertain, says Briegel. ‘But I think the resolution is now very high, and I am actually fairly convinced that this model closely approximates reality. That is what makes the research exciting and interesting.’

According to Briegel, the research contributes to our understanding of how bacteria move and navigate. Bacteria have sensors in their cell membrane that pick up chemical signals, which the bacterium can translate into a direction of rotation for its flagellum: rotating anticlockwise moves the cell steadily forward, whilst rotating clockwise causes the cell to tumble and thus reorientate. This gives rise to chemotaxis, allowing bacteria to move purposefully towards a target.

Briegel: ‘Changing the direction of rotation of the flagellum determines their path. A great many bacterial species are able to move using this system. It is also an important mechanism because some bacteria use flagella during an infection, including salmonella and the cholera bacterium.’

Chemosensors

Briegel’s research focuses primarily on the structure and function of chemosensors in the cell membranes of bacteria. According to Briegel, quite a lot is already known about how bacteria translate chemo-sensory information from their environment into the control of flagella. The relatively simple model bacterium E. coli in particular has already been mapped in considerable detail in this respect.

The challenge lies primarily in characterising the chemosensors of other pathogens, such as Spirochaetes, which cause Lyme disease and syphilis. ‘We are studying a bacterium from this group that causes gum disease. Spirochaetes have a different structure from other bacteria, as their cells are very elongated and slender, which means their chemosensors look different from those in E. coli.’

Knowledge of chemotaxis could offer a foothold for combating infections. As yet, however, there are no known clinical trials under way in this area, says Briegel. ‘You do read about that application quite often in grant applications. It would of course be rather wonderful if you could blind the chemo-sensory system of a bacterium, for instance by using substances that bind to the receptors on the cell surface.’

Also watch the video from our colleagues at Chemistry World about this research: