Cryptosporidium causes life threatening enteric disease in HIV-AIDS patients. Immunocompetent individuals are susceptible, but here symptoms are self-limiting. Cryptosporidium is also well known to cause diarrhea in small children. However, the full impact of Cryptosporidium on child mortality and morbidity was only recently appreciated. After rotavirus, Cryptosporidium is the most common pathogen responsible for severe diarrhea in children under 2 years. The main roadblock to achieving urgently needed advances is the overall poor tractability of Cryptosporidium in the laboratory. The goal of this project is to develop genetic tools for this parasite, and the effort builds on ou recent breakthrough in achieving transfection for C. parvum. Specifically, we will use the assay in hand to iteratively optimize transfection vectors and protocols for Cryptosporidium. We will devise strategies to select and isolate stable transgenic parasites from infected animals, and we will use these tools to establish a reporter model for Cryptosporidium. Such reporter pathogens will immediately open the disease to study and establish robust and quantitative correlates of infection, pathogenesis, drug cure, and immune-protection. In the long term, the ability to modify the parasite's genome will enable fundamental discovery and translate into tools and opportunities to treat and prevent cryptosporidiosis.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Research Project (R01)
Project #
Application #
Study Section
AIDS-associated Opportunistic Infections and Cancer Study Section (AOIC)
Program Officer
Joy, Deirdre A
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of Georgia
Public Health & Prev Medicine
Organized Research Units
United States
Zip Code
Pawlowic, Mattie C; Vinayak, Sumiti; Sateriale, Adam et al. (2017) Generating and Maintaining Transgenic Cryptosporidium parvum Parasites. Curr Protoc Microbiol 46:20B.2.1-20B.2.32
Szajnman, Sergio H; Galaka, Tamila; Li, Zhu-Hong et al. (2017) In Vitro and In Vivo Activities of Sulfur-Containing Linear Bisphosphonates against Apicomplexan Parasites. Antimicrob Agents Chemother 61:
Manjunatha, Ujjini H; Vinayak, Sumiti; Zambriski, Jennifer A et al. (2017) A Cryptosporidium PI(4)K inhibitor is a drug candidate for cryptosporidiosis. Nature 546:376-380
Hulverson, Matthew A; Vinayak, Sumiti; Choi, Ryan et al. (2017) Bumped-Kinase Inhibitors for Cryptosporidiosis Therapy. J Infect Dis 215:1275-1284
Arnold, Samuel L M; Choi, Ryan; Hulverson, Matthew A et al. (2017) Necessity of Bumped Kinase Inhibitor Gastrointestinal Exposure in Treating Cryptosporidium Infection. J Infect Dis 216:55-63
Sateriale, Adam; Striepen, Boris (2016) Beg, Borrow and Steal: Three Aspects of Horizontal Gene Transfer in the Protozoan Parasite, Cryptosporidium parvum. PLoS Pathog 12:e1005429
Vinayak, Sumiti; Pawlowic, Mattie C; Sateriale, Adam et al. (2015) Genetic modification of the diarrhoeal pathogen Cryptosporidium parvum. Nature 523:477-80