Toxoplasma gondii is an obligate intracellular parasite in the family Apicomplexa that infects a broad range of warm-blooded animals, including humans. This parasite is estimated to infect approximately one quarter of the world's human population and is capable of causing severe neurologic consequences and death in congenital infections or when reactivated in immunocompromised patients. Human infections result from ingestion of the environmentally resistant oocysts, through ingestion of undercooked meat from an intermediate host (e.g. swine, cattle, sheep) containing bradyzoite tissue cysts, or through congenital transmission. Recent evidence indicates that human infection through oocysts in water, soil or vegetables is a significant source of human infections and several waterborne outbreaks of toxoplasmosis have been reported globally. The oocyst stage is capable of persisting in the environment for years, remaining infective to humans and animals at an infectious dose as low as 1-10 oocysts. Domestic and wild felids are the only known definitive host in which sexual replication of the parasite occurs, resulting in excretion of oocysts in feces. A single cat may shed as many as 1 billion oocysts following a primary infection. Oocysts are resistant to methods used to disinfect water, including chlorination, UV irradiation and ozonation at levels well in excess of those used to treat both waste-water and sewage. The robustness of the oocyst is thought to come from the biochemical and structural properties of its bilayered oocyst wall. Yet, very little is known about the composition of the layers of the oocyst wall. The goal of this research plan is to describe the composition of the oocyst wall using the highly complementary proteomic and transcriptomic characterization of the oocyst wall to identify key proteins that confer properties of resistance. The K01 award would support Dr. Heather Fritz's career development as a postdoctoral DVM, PhD and prepare her for independent research. Dr. Fritz has a keen interest in zoonotic infectious disease and an eye to gain expertise in clinical veterinary microbiology and advanced biomedical research. Five years of mentored support is requested.
(provided by applicant): Toxoplasma gondii is a protozoal pathogen that chronically infects approximately one quarter of the world's total population and produces tragic neurologic consequences when acquired in utero or when reactivated in immunocompromised individuals. Waterborne transmission, through ingestion of the oocyst stage, is increasingly being recognized as a major source of human infection. The goal of this project is to understand the critical components in the oocyst that make it resistant to methods of water treatment, including chlorine, UV and ozone.
|VanWormer, Elizabeth; Fritz, Heather; Shapiro, Karen et al. (2013) Molecules to modeling: Toxoplasma gondii oocysts at the human-animal-environment interface. Comp Immunol Microbiol Infect Dis 36:217-31|
|Fritz, Heather M; Bowyer, Paul W; Bogyo, Matthew et al. (2012) Proteomic analysis of fractionated Toxoplasma oocysts reveals clues to their environmental resistance. PLoS One 7:e29955|
|Fritz, Heather M; Buchholz, Kerry R; Chen, Xiucui et al. (2012) Transcriptomic analysis of toxoplasma development reveals many novel functions and structures specific to sporozoites and oocysts. PLoS One 7:e29998|
|Buchholz, Kerry R; Fritz, Heather M; Chen, Xiucui et al. (2011) Identification of tissue cyst wall components by transcriptome analysis of in vivo and in vitro Toxoplasma gondii bradyzoites. Eukaryot Cell 10:1637-47|