Identifying components of Toxoplasma oocysts that confer environmental resistance

简介（由申请人提供）：刚地弓形虫是顶复虫科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。据估计，这种寄生虫感染了世界上大约四分之一的人口，在先天性感染或免疫功能低下患者中重新激活时，能够造成严重的神经系统后果和死亡。人类感染的原因是摄入了具有环境抗性的卵囊，摄入了含有慢殖子组织囊肿的中间宿主（如猪、牛、羊）未煮熟的肉，或通过先天性传播。最近的证据表明，通过水、土壤或蔬菜中的卵囊进行的人类感染是人类感染的一个重要来源，全球已报告了几次水传播的弓形虫病暴发。卵囊阶段能够在环境中持续数年，在感染剂量低至1-10个卵囊的情况下，对人类和动物仍具有传染性。家养和野生猫科动物是唯一已知的寄生虫有性繁殖的最终宿主，导致卵囊在粪便中排泄。一只猫在初次感染后可能会脱落多达10亿个卵囊。卵囊对用于水消毒的方法有抵抗力，包括氯化、紫外线照射和臭氧化，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，我们对卵囊壁各层的组成知之甚少。本研究计划的目标是利用卵囊壁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奖将支持希瑟·弗里茨博士作为博士后DVM，博士的职业发展，并为她的独立研究做好准备。Fritz博士对人畜共患传染病有着浓厚的兴趣，并致力于获得临床兽医微生物学和高级生物医学研究方面的专业知识。要求提供五年的指导支持。

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.