Clostridium difficile is a Gram positive, spore-forming rod that causes a spectrum of intestinal diseases extending from relatively mild diarrhea to toxic megacolon and is a frequent cause of hospital-acquired enteric infection. C. difficile associated disease (CDAD) generally occurs in hospitalized patients and almost always follows antibiotic treatment for unrelated infections. The incidence of CDAD has increased dramatically and C. difficile colitis has become one of the most important and expensive health-care associated infections. Recurrence rates after treatment are high. The role of the immune system in defense against this infection or in the pathogenesis of C. difficile-associated disease is poorly defined.
We are investigating a murine model of antibiotic-induced C. difficile colitis and are focusing on novel approaches to ameliorate infection and to decrease the intestinal pathology associated with CDAD. We find that flagellin treatment markedly increases survival of mice infected with C. difficile (Jarchum et al. Infection and Immunity 2011). Ongoing studies in the laboratory are determining the range of TLR agonists that can enhance resistance to C. difficile infection. We have also discovered that innate lymphocytes that produce interferon-gamma play an important role in early defense against acute C. difficile infection (Abt et al. Cell Host & Microbe 2015).
Ongoing studies in our laboratory are also identifying commensal bacterial species that confer resistance to C. difficile infection. We have recently identified Clostridium scindens, an obligate anaerobic bacterium that converts primary to secondary bile salts, as a major contributor to resistance against C. difficile colitis (Buffie et al. Nature 2015). Ongoing studies are focusing on identifying optimal commensal bacterial populations to maximize resistance to C. difficile infection.