Investigating the molecular basis of C. difficile-commensal interactions

Clostridium difficile, an anaerobic bacterial pathogen, causes C. difficile infection (CDI), is 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 is also a common cause of diarrhoea in piglets in several parts of the world. C. difficile infection is strongly influenced by the gut microbiota, and disruption of the healthy gut microbiota is usually necessary for C. difficile colonisation. Although C. difficile-microbiota interactions are critical in the establishment of infection as well as persistence within the gut within biofilms, interbacterial interactions between C. difficile and commensal bacteria are poorly understood. The goal of this project is to identify molecular mechanisms underpinning C. difficile interactions with commensal bacteria. We will utilise defined in vitro commensal communities to study the requirements for C. difficile survival within healthy microbiota. Proteins that are important for C. difficile-commensal interactions will be investigated further using in vitro human gut models and in vivo infection models. Identification of critical mechanisms that controls C. difficile microbiota interactions would be valuable for developing novel therapeutics and effective prophylactic strategies.