Toxigenic Clostridium difficile is the cause of essentially all cases of antibiotic-induced pseudomembranous colitis, a life-threatening disease, and the cause of approximately 40 percent of cases of antibiotic-induced diarrhea without intestinal inflammation. The present therapy for patients with C. difficile-associated intestinal disease is the administration of an antibiotic directed against C. difficile. However, there are problems with this current therapy including disease relapse, normal flora disruption, and antibiotic resistance. An alternative to antibiotic therapy of C. difficile- induced intestinal disease is the therapeutic use of bacteriophage. Recent studies indicate that bacteriophage can persist and multiply in tissue, blood and the intestinal tracts of animals and can be effective therapeutic and prophylactic agents. Preliminary experiments demonstrate that administration of bacteriophage to hamsters, treated with clindamycin and a toxigenic strain of C. difficile, prevents development of a fatal ileocecitis. It is the purpose of this research application to more rigorously examine these bacteriophage.
Specific Aim number 1 will isolate and characterize a collection of C. difficile bacteriophage with respect to their virulence and host-range so that the most effective phages for use in in vivo studies will be identified.
Specific Aim number 2 will examine in vivo properties of C. difficile bacteriophage and their efficacy in the treatment and prevention of C. difficile-associated intestinal disease employing a hamster animal model.
| Revathi, Govind; Fralick, Joe A; Rolfe, Rial D (2011) In vivo lysogenization of a Clostridium difficile bacteriophage ?CD119. Anaerobe 17:125-9 |
| Govind, Revathi; Vediyappan, Govindsamy; Rolfe, Rial D et al. (2009) Bacteriophage-mediated toxin gene regulation in Clostridium difficile. J Virol 83:12037-45 |
| Govind, Revathi; Vediyappan, Govindsamy; Rolfe, Rial D et al. (2006) Evidence that Clostridium difficile TcdC is a membrane-associated protein. J Bacteriol 188:3716-20 |
| Govind, Revathi; Fralick, Joe A; Rolfe, Rial D (2006) Genomic organization and molecular characterization of Clostridium difficile bacteriophage PhiCD119. J Bacteriol 188:2568-77 |
