Identifying components of Toxoplasma oocysts that confer environmental resistance
Principal Investigator: HEATHER MICHELLE FRITZ
Abstract: DESCRIPTION (provided by applicant: 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. PUBLIC HEALTH RELEVANCE (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.
Funding Period: 2011-01-01 - 2015-12-31
more information: NIH RePORT
- Methods to produce and safely work with large numbers of Toxoplasma gondii oocysts and bradyzoite cystsH Fritz
Department of Pathology, Microbiology and Immunology, School of Veterinary Medicine, 1 Shields Avenue, University of California Davis, CA 95616, USA
J Microbiol Methods 88:47-52. 2012..This procedure proved to completely inactivate oocysts without evidence of significant alteration of the oocyst molecular integrity...
- Proteomic analysis of fractionated Toxoplasma oocysts reveals clues to their environmental resistanceHeather M Fritz
Department of Pathology, Microbiology and Immunology, School of Veterinary Medicine, University of California Davis, Davis, California, United States of America
PLoS ONE 7:e29955. 2012..The latter are known from other systems to be key to enabling survival against desiccation...
- Transcriptomic analysis of toxoplasma development reveals many novel functions and structures specific to sporozoites and oocystsHeather M Fritz
Department of Pathology, Microbiology and Immunology, University of California Davis, School of Veterinary Medicine, Davis, California, United States of America
PLoS ONE 7:e29998. 2012..This work provides the first in-depth insight into the development and functioning of one of the most important but least studied stages in the Toxoplasma life cycle...
- Toxoplasma gondii sporozoites invade host cells using two novel paralogues of RON2 and AMA1Anna Poukchanski
Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, California, United States of America
PLoS ONE 8:e70637. 2013..These data indicate that sporozoites and tachyzoites each use a distinct pair of paralogous AMA1 and RON2 proteins for invasion into host cells, possibly due to the very different environment in which they each must function. ..
- Oklahoma Center for Respiratory and Infectious DiseasesLin Liu; Fiscal Year: 2013..The completion of the goals of the present COBRE will have a major impact on research programs on respiratory infectious diseases in the State of Oklahoma. ..
- Unique functions of the mitochondrial tRNA import machinety in T. gondiiLilach Sheiner; Fiscal Year: 2013..gondii mitochondrion and hence contribute to the design of new countermeasures, also of relevance to other apicomplexan parasites such as the causative agent of malaria, Plasmodium falciparum. ..
- Analysis of Toxoplasma sexual development in polarized cat intestinal cellsLaura J Knoll; Fiscal Year: 2013..Any progression through the sexual cycle of T. gondii in tissue culture will be a major advance for the field because a molecular analysis of these recalcitrant stages can begin. ..
- Center for Neuroplasticity at the University of Puerto RicoSteven N Treistman; Fiscal Year: 2013..This UPR COBRE Center should define pathways and benchmarks for basic and translational research across the UPR system for the next decades. ..
- New England Regional Center of Excellence in Biodefense and Emerging Infectious DDennis L Kasper; Fiscal Year: 2013..NERCE will also continue its Developmental Projects program and Career Development in Biodefense program in an effort to initiate new research efforts and to attract new investigators to this field. ..
- Toxoplasma gondii: cyst wallLouis M Weiss; Fiscal Year: 2013..Understanding this structure is important for the development of new strategies to eliminate latent infection and prevent reactivation toxoplasmosis. ..
- Southeast Regional Centers of Excellence for Biodefense &Emerging Infectious DiPhilip Frederick Sparling; Fiscal Year: 2013..SERCEB brings new investigators to the biodefense effort through a combination of educational programs, support of innovative new projects, and the synergistic interactions among its world-class investigators. ..