Infectious Diseases: Clostridium difficile infection
Clostridium difficile infection (CDI) causes antibiotic associated diarrhea and pseudomemberous colitis, mostly in the elderly and in hospitalized patients. The main cause of pathology is colonic expression of two large glucosylating toxins, TcdA and TcdB. Research in the Department of Infectious Diseases and Global Health aims to understand the mechanisms of toxin-mediated inflammation and to investigate the role of each toxin in the pathogenesis of C. difficile-associated diseases. The Department is developing CDI models in the gnotobiotic pig model transplanted with the human microbiome and generating recombinant CDI vaccines. In addition, we are evaluating antimicrobial agents and immune based therapies, including the Merck human monoclonal antibodies and hyperimmune bovine colostrum, to treat and/or prevent CDI disease. Finally, we are developing recombinant antitoxin therapies for the treatment of CDI using our technology which is described in more detail on the Recombinant Antitoxins page.
Publications
- Steele J, Sponseller J, Schmidt D, Cohen O, Tzipori S. 2013. Hyperimmune bovine colostrum for treatment of GI infections: A review and update on Clostridium difficile. Hum Vaccin Immunother. 9(7). [Epub ahead of print]. PMID:23435084
- Steele J, Mukherjee J, Parry N, Tzipori S.. 2013. Antibody against TcdB, but not TcdA, prevents development of gastrointestinal and systemic Clostridium difficile disease. J Infect Dis. 207:323-30. PMID:23125448
- Butler MM, Shinabarger DL, Citron DM, Kelly CP, Dvoskin S, Wright GE, Feng H, Tzipori S, Bowlin TL. 2012. MBX-500, a hybrid antibiotic with in vitro and in vivo efficacy against toxigenic Clostridium difficile. Antimicrob Agents Chemother. 564786-92. PMID:22733075
- Wang H, Sun X, Zhang Y, Li S, Chen K, Shi L, Nie W, Kumar R, Tzipori S, Wang J, Savidge T, Feng H. 2012. A chimeric toxin vaccine protects against primary and recurrent Clostridium difficile infection. Infect Immun. 80:2678-88. PMID:22615245
- Steele J, Chen K, Sun X, Zhang Y, Wang H, Tzipori S, Feng H. 2012. Systemic dissemination of Clostridium difficile toxins A and B is associated with severe, fatal disease in animal models. J Infect Dis. 205:384-91. PMID:22147798
- Sun X, Wang H, Zhang Y, Chen K, Davis B, Feng H. 2011. Mouse relapse model of Clostridium difficile infection. Infect Immun. 79:2856-64. PMID: 21576341
- Steele J, Feng H, Parry N, Tzipori S. 2010. Piglet models of acute or chronic Clostridium difficile illness. Infect Dis. 201:428-34. PMID: 20039803
- Sun X, Savidge T, Feng H. 2010. The enterotoxicity of Clostridium difficile toxins. Toxins (Basel). 2:1848-80. PMID:22069662
- He X, Wang J, Steele J, Sun X, Nie W, Tzipori S, Feng H. 2009. An ultrasensitive rapid immunocytotoxicity assay for detecting Clostridium difficile toxins. J Microbiol Methods. 78:97-100. PMID:19393695
- Sun X, He X, Tzipori S, Gerhard R, Feng H. 2009. Essential role of the glucosyltransferase activity in Clostridium difficile toxin-induced secretion of TNF-alpha by macrophages. Microb Pathog. 46:298-305. PMID:19324080
- He X, Sun X, Wang J, Wang X, Zhang Q, Tzipori S, Feng H. 2009. Antibody-enhanced, Fc gamma receptor-mediated endocytosis of Clostridium difficile toxin A. Infect Immun. 77:2294-303. PMID:19307220
- Yang G, Zhou B, Wang J, He X, Sun X, Nie W, Tzipori S, Feng H. 2008. Expression of recombinant Clostridium difficile toxin A and B in Bacillus megaterium. BMC Microbiol. 8:192. PMID:18990232