Identifying components of Toxoplasma oocysts that confer environmental resistance

描述(申请人提供：弓形虫是尖端复合体家族中的一种专性细胞内寄生虫，感染包括人类在内的各种温血动物。据估计，这种寄生虫感染了世界上大约四分之一的人口，并能够在先天性感染或免疫功能低下的患者中重新激活时，导致严重的神经系统后果和死亡。人类感染是由摄取耐环境卵囊、从含有缓殖子组织囊的中间宿主(例如猪、牛、羊)摄取未煮熟的肉类或通过先天性传播引起的。最近的证据表明，通过水、土壤或蔬菜中的卵囊感染人类是人类感染的一个重要来源，全球已报告了几起通过水传播的弓形虫病暴发。卵囊阶段能够在环境中持续多年，以低至1-10个卵囊的感染剂量对人和动物保持感染。家猫和野生猫科动物是已知的唯一确定的宿主，在这些宿主中，寄生虫发生有性复制，导致卵囊从粪便中排出。一只猫在初次感染后可能会排出多达10亿个卵囊。卵囊对用于水消毒的方法具有抵抗力，包括氯化、紫外线照射和臭氧氧化，其水平远远超过用于处理废水和污水的方法。卵囊的健壮性被认为来自其双层卵囊壁的生化和结构特性。然而，人们对卵囊壁层的组成知之甚少。这项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。K01奖项将支持希瑟·弗里茨博士作为博士后DVM和博士的职业发展，并为她的独立研究做好准备。弗里茨博士对人畜共患传染病有着浓厚的兴趣，并着眼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。需要五年的指导支持。 公共卫生相关性(由申请人提供)：弓形虫是一种原生动物病原体，慢性感染约四分之一的世界总人口，当在子宫内感染或在免疫功能受损的人中重新激活时，会产生悲惨的神经系统后果。通过摄入卵囊阶段的水媒传播越来越被认为是人类感染的一个主要来源。该项目的目标是了解卵囊中使其对包括氯、紫外线和臭氧在内的水处理方法具有抵抗力的关键成分。

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.