Developing in vitro co-culture systems for investigating Clostridium difficile-host interactions

Year of award: 2015


  • Dr Meera Unnikrishnan

    University of Warwick

Project summary

Clostridium difficile is a major cause of gastrointestinal infections in hospital settings. C. difficile colonises the human gut when there is an alteration in gut microbiota, usually after antibiotic therapy. The interactions of the bacterium with the host gut cells are of critical importance to infection, yet we know little about how the bacterium attaches, colonises and persists in the gut during infection. A major hurdle in studying host-bacterial interactions is the difficulty of in vitro investigation of this anaerobic bacterium with gut epithelial cells that require oxygen. 

We aim to establish in vitro diffusion chamber infection systems that will allow simultaneous culture of bacteria and intestinal cells under dual environmental conditions. These co-culture models will be valuable tools for studying multiple aspects of clostridial pathogenesis, including bacterial attachment, invasion, micro-colony formation, alongside the local host cell responses to C. difficile infection. We will use these tools to identify and investigate functions of novel C. difficile proteins and processes that mediate gut colonisation.

Robust in vitro systems that mimic the gut environment and allow examination of host-clostridial interactions will be an excellent technical resource for future research into C. difficile.