BBSRC White Rose DTP Studentship - Structures and mechanisms in killing of Clostridioides (Clostridium) difficile by bacteriophages

Clostridioides difficile (C. difficile) causes serious illness and even death. Many common antibiotics inadvertently kill the beneficial bacteria in the human gut but have no effect on C. difficile; indeed they actually benefit the bacterium by removing competition.

The C. difficile surface is coated in a protein S-layer that normally serves to protect the cell. An alternative to antibiotics might be to use therapeutic particles that attach to the S-layer to kill the cell. These particles would have features in common with viruses that infect the cell. If we can understand how these viruses attack the cell, we will be able to design more efficacious therapeutic particles.

We do not know how viruses recognise the S-layer, where they bind, what changes they undergo while binding, nor how they penetrate the cell envelope to kill the cell. This multidisciplinary project will apply state of the art techniques of structural and molecular biology to address these questions. We will exploit exciting new developments in cryoelectron microscopy (CryoEM)- single particle EM and electron cryotomography. We will create exquisitely detailed 3D images of the host cell with bacteriophages revealed in all the steps from initial cell surface binding to cell penetration and subsequent killing.