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Identifying components of Toxoplasma oocysts that confer environmental resistance

识别弓形虫卵囊中具有环境抵抗力的成分

基本信息

批准号：
8788454
负责人：
Heather Michelle Fritz
金额：
$ 11.49万
依托单位：
WASHINGTON STATE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2011
资助国家：
美国
起止时间：
2011-01-01 至 2015-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8788454
关键词：
Amino Acids Animals Apicomplexa Biochemical Biological Biomedical Research Birds Bleomycin Blood Brain Candidate Disease Gene Cattle Cessation of life Chemicals Chlorine Clinical Communicable Diseases Cyst Data Detection Development Disease Outbreaks Doctor of Philosophy Dose Environment Environmental Pollution Excretory function Eye Family Family Felidae Family suidae Feces Felis catus Foundations Gene Expression Profiling Genes Genetic screening method Glass Goals Harvest Health Histologic Human Immunocompromised Host In Vitro Individual Infection Ingestion Knock-out Lead Mammals Mass Spectrum Analysis Meat Mentored Research Scientist Development Award Mentors Methods Microbiology Mus Neurologic Oocysts Ozone Parasites Population Preparation Prevalence Property Proteins Proteomics Protozoa RNA Reagent Reporting Research Resistance Sampling Sewage Sheep Soil Source Sporozoites Staging Staging System Testing Thick Time Tissues Toxoplasma Toxoplasma gondii Toxoplasmosis Tyrosine Vegetables Water Water Pollution Work career development chlorination congenital infection crosslink improved in utero interest novel obligate intracellular parasite pathogen transcriptomics transmission process ultraviolet irradiation undercooked wasting water treatment waterborne

项目摘要

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.

描述（由申请人提供：弓形虫是顶复门中的一种专性细胞内寄生虫，可感染包括人类在内的多种温血动物。这种寄生虫估计感染世界上大约四分之一的人口，并且能够在先天性感染或在免疫功能低下的患者中重新激活时造成严重的神经系统后果和死亡。人类感染是由通过摄入来自含有缓殖子组织包囊的中间宿主（例如猪、牛、羊）的未煮熟的肉，或通过先天性传播，摄入具有耐环境性的卵囊。最近的证据表明，人类通过水、土壤或蔬菜中的卵囊感染是人类感染的一个重要来源，全球已报告了多起水源性弓形虫病疫情。的卵囊阶段能够在环境中持续存在多年，在低至 1-10 个卵囊的感染剂量下仍对人类和动物具有感染性。家养和野生猫科动物是唯一已知的寄生虫发生有性复制的最终宿主，导致卵囊随粪便排出。一只猫在初次感染后可能会排出多达 10 亿个卵囊。卵囊对水消毒方法具有抵抗力，包括氯化、紫外线照射和臭氧处理，其水平远远超过用于处理废水和污水的方法。卵囊的坚固性被认为来自其双层卵囊壁的生化和结构特性。然而，人们对卵囊壁各层的组成知之甚少。本研究计划的目标是使用卵囊壁的高度互补的蛋白质组学和转录组学特征来描述卵囊壁的组成，以确定赋予抗性特性的关键蛋白质。 K01 奖将支持 Heather Fritz 博士作为博士后 DVM、PhD 的职业发展，并为她进行独立研究做好准备。 Fritz 博士对人畜共患传染病有着浓厚的兴趣，并希望获得临床兽医方面的专业知识微生物学和先进的生物医学研究。需要五年的指导支持。