Clostridioides difficile, the etiology of pseudomembranous colitis, causes substantive morbidity, mortality and close to $5 billion/year in US healthcare costs. Commensals provide primary protection against C. difficile infections though the underlying mechanisms of action remain ill-defined. We have identified individual bacterial species that provide long-term survival against virulent C. difficile strains, and other species that can make the infection worse. Our proposed aims will define specific commensal activities and commensal genes mediating these effects on the pathogen, and test their functions in vivo, in mice carrying mouse vs human complex microbiota, for the purposes of developing defined bacteriotherapeutics and biomarkers to predict successful therapy.
Clostridioides difficile causes severe infections of the colon, infections that commonly arise after use of antibiotics that destroy healthy populations of microbes which prevent infection. Our proposed studies are defining the specific microbes that provide this protection, and their mechanisms of action. This knowledge will be used to help create more defined, effective and safe therapies for this disease.
