Molecular mechanisms underlying Campylobacter jejuni's unusual swimming style

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Campylobacter jejuni is a bacterium that causes food poisoning. In the UK Campylobacter causes more food poisoning than other bacteria such as E. coli or Salmonella (e.g, the Food Standards Agency estimates that Campylobacter infections cost us almost one billion pounds per year). Campylobacter is also very similar to other 'dangerous' bacteria that cause other stomach problems, including cancers. If we can understand these bacteria better, we'll be better able to develop drugs to fight them. This grant proposal uses Campylobacter as an example to understand swimming in this family of dangerous bacteria.Most dangerous bacteria need to be able to swim to cause their disease, and Campylobacter swims in a very unusual manner. Most bacteria 'swim' using a miniature motor that sits in the skin of the bacterium. On the end of the motor's driveshaft is a long tail that the motor spins; the spinning long tail curls up to become a helical propeller, pushing the bacterium through its liquid habitat. Campylobacter (and family members) uses the same tail but swims in a very different way to other bacteria, and this may prove to be its Achilles heal: we may be able to develop targeted drugs that only affect Campylobacter and family. Specifically, Campylobacter uses a single very powerful motor to swim. It also uses this powerful motor to rotate its body, which is shaped like a corkscrew, allowing it to 'bore' into very thick fluids such as gut mucous easily, and therefore is better able to cause disease. But we don't understand how Campylobacter is able to do many of these things. If we can better understand the biology of this curious swimming we may be able to make drugs to prevent it.To understand bacterial swimming, it's really important to be able to see the motor and the shapes of the cell, which is a difficult task. I believe this is absolutely essential, so to visualize bacteria I trained in a technique that enables us to directly see them inside the cell, and the molecular details of the motor that drives swimming. To help me fully understand the images from this project I've recruited a stellar team of international scientists.We're still some way from using these results to fight Campylobacter food poisoning. If we had a detailed understanding of how Campylobacter swims, however, we might start designing drugs that stop it swimming. This MRC proposal requests funds to perform this research.I propose four aims:One: Campylobacter actually makes two motors, but only uses one of them (if it used both, they'd push in opposite directions!). I'll use my imaging skills to see both the active and inactive motors to understand what the difference is - in turn, telling us how it works. If we can understand how one motor is inactivated, maybe we can make drugs to inactivate both motors?Two: Campylobacter swims by rotating both its tail, and its cell body. I think I know how it divides the amount of swimming power between the two, and will test this.Three: How does Campylobacter make itself helical-shaped? I'll collect images to make progress towards understanding this.Four: Finally, I'll team up with collaborators to develop a mathematical model to combine all previous results to understand how all factors combine to produce the unique swimming of Campylobacter.