Assessment of Zoonotic Risk of Emerging Infections in Companion Animals

伴侣动物新发感染的人畜共患风险评估

• 批准号: 10478898
• 负责人: Laura Brunengraber Goodman
• 金额: $ 21.89万
• 依托单位: CORNELL UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-15 至 2025-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10478898
• 关键词: Assessment; Zoonotic; Risk; Emerging; Infections

Project Summary/Abstract This project evaluates the zoonotic implications of two important possible pathogens of companion animals: E. coli and coronaviruses. E. coli is the most common pathogen tested for antibiotic susceptibility in veterinary diagnostic labs. It is also one of the most concerning for multi-drug resistance; several isolates captured thus far in Vet-LIRN active surveillance are predicted to be pan-resistant to all drugs used in human or animal medicine. Our group has published the first animal host specific E. coli virulence database compatible with tools that can mine whole genome sequencing data. We now propose a comparative evolutionary genomic study to assess the potential of E. coli in dogs to encode novel resistance mechanisms and cause disease in humans. The data will be explored employing the latest developments in bacterial pan- genomic analysis, as well as bacterial GWAS. Such analysis will reveal if there are E. coli loci adapted to dogs, whether such loci have the functional character suggestive of pathogenic potential, and whether dogs may be a reservoir of potential pathogenesis or antibiotic resistance. The present outbreak of coronavirus disease caused by SARS-CoV-2 (COVID-19) is the third documented spillover of an animal coronavirus to humans to have resulted in a major epidemic, within the past two decades. Characterizing the species diversity of coronaviruses from companion animals, represents an important necessary step towards improving our understanding of virus–host interactions and to enhance our preparedness for future outbreaks. We will undertake this characterization in three different host species – horses, cats, and dogs – making use of an extensive set of time series samples (respiratory and feces) that comprise the AHDC’s collection. Sequences of coronavirus genomes will be acquired using two approaches: RNAseq of the respiratory virome and multiplexed amplicon approaches of both respiratory and feces samples; the former will allow us to identify the coronavirus species repertoire of each host, including the identification of any new coronavirus species, the latter will provide the ability to explore aspects of diversity in detail, within and between hosts. Comparative evolutionary genomic analyses of the data will inform on a wide variety of issues related to their zoonotic potential, including for example: (1) Which coronavirus species are more prone to inter-host transmission and is there a directionality to that transmission? (2) Are their host reservoirs for any of the virus species? (3) Which have a history of recombination? (4) Which have a history of molecular adaptation and what viral proteins does that involve? Our final aim is to provide eight other Vet-LIRN sequencing laboratories with the reagents and training to be able to independently sequence and analyze bacterial and viral genomes, including SARS-CoV-2. All three Aims of this project directly support the mission of the FDA to ensure the safety of our nation's food supply and protect public health.

项目概要/摘要 该项目评估了两种重要的可能伴生病原体的人畜共患病影响 动物：大肠杆菌和冠状病毒。大肠杆菌是抗生素敏感性测试中最常见的病原体 兽医诊断实验室。它也是最令人担忧的多重耐药性之一；几个分离株 迄今为止在 Vet-LIRN 主动监测中捕获的药物预计对人类使用的所有药物具有泛耐药性 或动物药。我组发表第一个动物宿主特异性大肠杆菌毒力数据库 与可以挖掘全基因组测序数据的工具兼容。我们现在提出一个比较 进化基因组研究评估狗体内大肠杆菌编码新耐药机制的潜力 并引起人类疾病。将利用细菌泛素的最新进展来探索这些数据 基因组分析，以及细菌 GWAS。这样的分析将揭示是否有适合狗的大肠杆菌基因座， 这些位点是否具有提示致病潜力的功能特征，以及狗是否可能是 潜在发病机制或抗生素耐药性的储存库。 目前由 SARS-CoV-2 (COVID-19) 引起的冠状病毒病的爆发是第三次 有记录显示，动物冠状病毒在过去传播给人类，导致了一场重大流行病 二十年。表征来自伴侣动物的冠状病毒的物种多样性，代表了 提高我们对病毒与宿主相互作用的理解并增强我们的认识的重要必要步骤 为未来爆发做好准备。我们将在三种不同的宿主物种中进行这种表征—— 马、猫和狗——利用大量时间序列样本（呼吸和粪便） 包括 AHDC 的收藏。冠状病毒基因组序列将通过两种方法获得： 呼吸道病毒组的 RNAseq 以及呼吸道和粪便样本的多重扩增子方法； 前者将使我们能够识别每个宿主的冠状病毒物种库，包括识别 对于任何新的冠状病毒物种，后者将提供详细探索多样性方面的能力，在 以及主机之间。数据的比较进化基因组分析将提供多种信息 与其人畜共患潜力相关的问题，包括例如：（1）哪些冠状病毒物种更容易发生 主机间传输以及该传​​输是否有方向性？ (2) 它们的宿主水库是否存在任何 病毒种类？ (3) 哪些有重组历史？ (4)有分子历史 适应以及其中涉及哪些病毒蛋白？ 我们的最终目标是为其他八家 Vet-LIRN 测序实验室提供试剂和培训 能够独立测序和分析细菌和病毒基因组，包括 SARS-CoV-2。全部 该项目的三个目标直接支持 FDA 确保我国食品安全的使命 供给并保障公众健康。