Microsporidiosis is clearly an important group of emerging pathogens. Research on the human pathogen Enterocytozoon bieneusi has been hampered both by a lack of in vivo animal models as well as in vitro cultivation systems. A model of E. bieneusi has been established in which both human and simian isolates of E. bieneusi have been transferred successfully to immunosuppressed gnobiotic (GB) piglets by infection them with spores of E. bieneusi stored for as long as two years at 4 degrees Centigrade. In addition, transmission has been successful from piglet to piglet. The goal of this research is to characterize the immunosuppressed GB piglet model of E. bieneusi for the evaluation of antimicrobial agents against this parasite. The course of infection will be studied, including some fundamental aspects of parasite biology and its interaction with the host cell. Information is lacking due to an absence of animal models.
The specific aims are: To characterize E. bieneusi infection in the GB immunosuppressed piglet model. To study the course of infection, clinical manifestation, and pathogenesis. To determine the relationship between immunosuppression and extent of infection to optimize the model. To study early events in host cell pathogen interaction at the ultrastuctural level. To optimize standardize and validate the immunosuppressed GB piglet model for preclinical testing of therapeutic formulations against E. bieneusi with a view of testing five per year for Years 2-5 of the support period. The hypothesis is that the GI tract in piglets and humans have similar immune responses to this infection and that pigs represent a good animal model of this disease. The development of this model is the focus of this application, not basic advances in biology. This model will be of immediate use for drug testing and also as a source of E. bieneusi spores for antibody development (diagnostics) and basic biology. The development of this porcine model would provide an invaluable source of parasitic material for additional investigations and accelerate research on this organism. Given the cost and nature of the simian SIV model it is unlikely this model would serve the same function.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
1R01AI043196-01
Application #
2649736
Study Section
Special Emphasis Panel (ZRG5-ARRB (02))
Project Start
1998-05-01
Project End
2003-04-30
Budget Start
1998-05-01
Budget End
1999-04-30
Support Year
1
Fiscal Year
1998
Total Cost
Indirect Cost
Name
Tufts University
Department
Biochemistry
Type
Schools of Medicine
DUNS #
604483045
City
Boston
State
MA
Country
United States
Zip Code
02111
Feng, Xiaochuan; Akiyoshi, Donna E; Sheoran, Abhineet et al. (2006) Serial propagation of the microsporidian Enterocytozoon bieneusi of human origin in immunocompromised rodents. Infect Immun 74:4424-9
Sheoran, Abhineet S; Feng, Xiaochuan; Kitaka, Sabrina et al. (2005) Purification of Enterocytozoon bieneusi from stools and production of specific antibodies. J Clin Microbiol 43:387-92
Sheoran, Abhineet S; Feng, Xiaochuan; Singh, Inderpal et al. (2005) Monoclonal antibodies against Enterocytozoon bieneusi of human origin. Clin Diagn Lab Immunol 12:1109-13
Lui, Vivian Wai Yan; He, Yukai; Falo, Louis et al. (2002) Systemic administration of naked DNA encoding interleukin 12 for the treatment of human papillomavirus DNA-positive tumor. Hum Gene Ther 13:177-85
Tumwine, James K; Kekitiinwa, Addy; Nabukeera, Nicolette et al. (2002) Enterocytozoon bieneusi among children with diarrhea attending Mulago Hospital in Uganda. Am J Trop Med Hyg 67:299-303
Buckholt, Michael A; Lee, John H; Tzipori, Saul (2002) Prevalence of Enterocytozoon bieneusi in swine: an 18-month survey at a slaughterhouse in Massachusetts. Appl Environ Microbiol 68:2595-9
Lui, V W; Falo Jr, L D; Huang, L (2001) Systemic production of IL-12 by naked DNA mediated gene transfer: toxicity and attenuation of transgene expression in vivo. J Gene Med 3:384-93
Sestak, K; Lee, J H; Brisben, J et al. (2000) Tacrolimus-FK506 induced immunosuppression in gnotobiotic piglets. Vet Immunol Immunopathol 77:289-300