Comprehensive characterization of parasite and commensal assemblages in humans

人类寄生虫和共生组合的综合表征

• 批准号: 10554346
• 负责人: Tony L. Goldberg
• 金额: $ 19.44万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-01-24 至 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10554346
• 关键词: Affect; Animals; Antigens; Antiparasitic Agents; Bacteria; Bacteriology; Bar Codes; Bioinformatics; Biological Assay; Biology; Blood; Communities; Custom; DNA; DNA sequencing; Data; Data Analyses; Data Set; Databases; Detection; Development; Diagnostic; Digestion; Disadvantaged; Disease; Disease Outcome; Ecology; Equilibrium; Eukaryota; Formalin; Future; Goals; Health; Helminths; Human; Immunity; In Vitro; Industry Standard; Intestinal parasite; Knowledge; Lead; Literature; Medicine; Metagenomics; Methodology; Methods; Microscopic; Microscopy; Molecular; Morbidity - disease rate; Noise; Organism; Parasites; Parasitic Diseases; Parasitic infection; Parasitology; Pathogenicity; Performance; Persons; Play; Population; Predictive Value; Preparation; Process; Prokaryotic Cells; Protocols documentation; Protozoa; Publishing; Reagent; Research; Research Methodology; Resolution; Risk; Role; Sampling; Specificity; Standardization; Structure; Taxonomy; The science of Mycology; Therapeutic; Tissues; Virus; Work; analysis pipeline; bacterial community; bacteriome; bioinformatics pipeline; design; detection method; diagnostic tool; disorder risk; dysbiosis; fungal microbiota; fungus; high risk population; human disease; improved; in silico; insight; microbiome; mortality; mycobiome; novel; pathogen; prevent; symbiont; tool; user-friendly

PROJECT SUMMARY/ABSTRACT Diseases attributed to parasites cause substantial morbidity and mortality globally. However, there is mounting evidence that the relationship between humans and symbionts (defined here as all host-dependent eukaryotic organisms, including parasites and commensals) is not always detrimental and, in fact, may sometimes confer important health advantages. Symbiont assemblages may aid in digestion, confer protective immunity, or, paradoxically, provide protection from pathogenic parasite infection and disease. We currently understand the biology and ecology of eukaryotic parasites that cause human disease, but we know very little about the overall structure and function of communities of protozoans and helminths that also colonize humans. This shortcoming hinders progress in the field of parasitology, compared to the fields of bacteriology and mycology, which have revolutionized our understanding of human health through the study of bacterial and fungal microbiota. Indeed, most current parasitological methods are designed for a different purpose: to target specific, pathogenic organisms. Although methods for unbiased community analysis have been validated and standardized for prokaryotes and fungi, no such methods currently exist for eukaryotic symbionts, including parasites. With no standardized methods in place, research into the beneficial effects of eukaryotic symbiont communities and their potential role in parasitic disease represents a critical knowledge gap. The ultimate objective of this work is to create a uniform, validated research tool for the study of human symbiont assemblages, comparable to what has been achieved for the bacterial and fungal microbiomes. To this end, we have developed a novel comprehensive (able to identify all organisms regardless of prior characterization, including novel organisms) assay for eukaryotic symbiont assemblage characterization that is based on newly-designed PCR primers, a novel noise reduction strategy, and a user- friendly bioinformatic pipeline. Our goals in developing this assay were to 1) create an “industry standard” for symbiont community assessment, analogous to other standardized microbiome assays, 2) develop a broadly- applicable research method useful for all organisms and all sample types, 3) contribute to our understanding of the basic biology and ecology of human eukaryotic symbiont communities and 4) inform future development of “universal” diagnostic tools and targeted anti-parasitic therapeutics. We will optimize the assay in silico using custom databases, in vitro using a “mock community”, and ex vivo using samples from experimentally-infected animals. We will then validate the pipeline and assess its performance by analyzing human samples from two different populations in which intestinal parasites have previously been characterized by microscopy and PCR. Through completion of this project, we hope to provide a critically-needed research tool that will improve our understanding of human symbiont communities, and that, in turn, will inform advances in human health and medicine.

项目摘要/摘要 归因于寄生虫的疾病在全球范围内引起大量的发病率和死亡率。但是，有安装 人类与符号之间的关系的证据（此处定义为所有宿主依赖的真核生物 包括寄生虫和共生在内的有机体并不总是有害，实际上有时可能会召集 重要的健康优势。共生组合可能有助于消化，会议保护性免疫学或 矛盾的是，可保护致病性寄生虫感染和疾病。我们目前了解 引起人类疾病的真核寄生虫的生物学和生态学，但我们对总体知识了解甚少 原生动物和蠕虫的群落的结构和功能也使人类定居。这 与细菌学和真菌学领域相比，缺点在寄生虫学领域的进展， 通过研究细菌和真菌，这彻底改变了我们对人类健康的理解 微生物群。实际上，大多数当前的寄生方法都是为了一个不同的目的而设计的： 特异性的，致病的生物。尽管公开社区分析的方法已得到验证，并且 针对原核生物和真菌进行标准化，目前没有这样的真核符号的方法，包括 寄生虫。没有标准化的方法，研究真核的有益作用 符号社区及其在寄生疾病中的潜在作用代表了一个关键的知识差距。 这项工作的最终目的是创建一个统一的，经过验证的研究工具进行研究 人类符号组合，与细菌和真菌所取得的成就相当 微生物组。为此，我们开发了一种新颖的全面（能够识别所有生物 无论先前的表征如何，包括新生物）真核符号组合 基于新设计的PCR引物，新型降噪策略和用户的表征 友好的生物信息学管道。我们开发该测定法的目标是1）为 共生社区评估，类似于其他标准化微生物组测定法，2） 适用的研究方法适用于所有生物和所有样本类型，3）有助于我们对 人类真核象征主义社区的基本生物学和生态学和4）信息未来的发展 “通用”诊断工具和靶向抗寄生虫治疗。我们将使用 自定义数据库，在体外使用“模拟社区”，并在体内使用实验感染的样品 动物。然后，我们将通过分析两个人的样本来验证管道并评估其性能 先前已经通过显微镜和PCR表征的肠道寄生虫的不同种群。 通过完成该项目，我们希望提供急需的研究工具，以改善我们的 了解人类共生群落，这反过来将为人类健康的进步提供信息 药品。