Investigating host - pathogen interactions associated with Clostridioides difficile colonisation and infection

Clostridioides difficile is a major cause of gastrointestinal infections in humans and animals. It is the leading cause of diarrheoa in piglets in many parts of the world. In recent years it has become evident that animal reservoirs of this pathogen that are important for human infections. A recent rise observed in community-acquired C. difficile infection, most likely attributed to the reservoirs that exist in the environment, as well as the increasing prevalence of hyper-virulent strains means we need to further our understanding of the molecular mechanisms that govern the pathogenesis of C. difficile. Colonisation of the gut is a key determinant of bacterial carriage and disease outcome, although little is known about bacterial or host factors modulating interactions between C. difficile and the gut epithelium. The gaps in our understanding can be attributed in part to the lack of tools that accurately represent the gut environment, whilst allowing real-time tracking of the progression of infection. Therefore, the aim of this project is to define the genes and proteins that are key to the colonisation and establishment of a C. difficile infection through the development of new in vitro fluidic gut models that can be combined with next generation sequencing techniques to elucidate the underpinning mechanisms. Identification and functional analysis of proteins critical to C. difficile colonisation will enhance our understanding of the establishment of pathogen in this gut and lead to effective interventions for CDI.