About the Project
Clostridium difficile, an anaerobic bacterial pathogen, causes C. difficile infection (CDI), a major healthcare-associated challenge worldwide. It is a leading cause of hospital associated diarrhoea with high rates of infection in the elderly. C. difficile has also been isolated from multiple animal hosts and is a common cause of diarrhoea in piglets in several parts of the world. The strains that cause disease in pigs were found identical to human isolates, indicating an animal reservoir of C.…
difficile. Community-acquired CDI has been on the rise in recent years, and studies have suggested that livestock via the environment and/or food.
Initial establishment of C. difficile in the gut is a key step in CDI pathogenesis. However, unlike other enteric pathogens, molecular interactions between C. difficile and the gut epithelium are poorly understood. Only a few host pathways activated during infection have been identified. Host cell receptors that the major C. difficile toxins A and B bind to and some epithelial and innate responses to infection for e.g.IL-33 have been well studied. However, other aspects of infection, such as C. difficile interactions with the colonic mucus layer or with the immune cells in the colon remain largely unexplored. A better understanding of the immune response to C. difficile and understanding C. difficile survival strategies in the gut are crucial for developing novel therapeutics, effective prophylactic strategies and improved diagnostic tools for CDI.
The goal of this study is to characterise C. difficile factors and host immune pathways activated by these during C. difficile infection using in vitro and ex vivo controlled environment models that we have developed in our laboratory to model the human gut bacterial interface. Elucidating specific pathways involved during initial infection will enhance our understanding of how this pathogen survives in the gut.
