Dissecting Mechanisms of Host Manipulation by Pathogens

剖析病原体操纵宿主的机制

• 批准号: 7221372
• 负责人: NOAH K WHITEMAN
• 金额: $ 4.68万
• 依托单位: HARVARD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-03-01 至 2010-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7221372
• 关键词: Acids; Address; Arabidopsis; Attention; Biological Assay; Biological Models; Characteristics; Communicable Diseases; Complex; Disease; Ecology; Ethylene; Ethylenes; Evolution; Figs - dietary; Gene Expression; Genes; Genetic; Genetic Models; Goals; Host Defense; Human; Infection; Infectious Agent; Insecta; Laboratories; Left; Link; Mastication; Mediating; Mission; Modeling; Molecular; Natural Immunity; Nature; Parasites; Pathogenesis; Pathway interactions; Physiological; Plant Growth Regulators; Plants; Predisposition; Production; Pseudomonas; Pseudomonas syringae; Public Health; Regulatory Pathway; Research; Research Personnel; Research Training; Resistance; Role; Salicylic Acid; Salicylic Acids; Signal Pathway; Signal Transduction; System; United States National Institutes of Health; Virulence; Virulence Factors; Virulent; analog; base; career; conditioning; coronafacic acid; coronatine; defense response; design; insight; jasmonate; jasmonic acid; methyl jasmonate; novel; pathogen; plant poison; research study; response; secondary infection; vector

DESCRIPTION (provided by applicant): Understanding the mechanisms by which infectious agents cause disease has been revolutionized through the use of model genetic systems, especially in the case of plant pathogens. Evolutionary biologists have also provided significant insight into our understanding of infectious disease dynamics, including the evolution of virulence. Although hosts in nature are attacked by multiple pathogens and parasites simultaneously, such interactions are rarely studied by molecular biologists since most studies focus on a single pathogen. Conversely, although organismal biologists study these interactions with the goal of uncovering general principles underlying the ecology and evolution of host-parasite interactions, the underlying genetic or mechanistic bases of the biotic interactions mediated by host defense responses are rarely characterized. Thus, public health researchers have joined with evolutionary biologists in an effort to better understand and control infectious diseases. This proposal presents experiments designed to characterize proximate (genetic/physiological/mechanistic) and ultimate (evolutionary) mechanisms underlying two types of host defense signaling manipulation by pathogens in a model three-way pathosystem involving Arabidopsis, the pathogen Pseudomonas syringae (Ps) and insect herbivores. Ps manipulates defense signaling cross talk leading to systemic induced susceptibility (SIS) to infection by the same pathogens and increased resistance or susceptibility (SIS) to herbivory. SIS to Ps is mediated by the jasmonic acid analog coronatine (COR), which is produced by virulent Ps. However, the signal mediating the SIS to herbivory is unknown, and in both cases, the genes underlying systemic signals in the host plant are unknown. In the first aim, I will build on preliminary gene expression experiments to characterize the pathways underlying both types of SIS. In the second aim, I will investigate whether there is an adaptive basis to the two types of SIS by conducting kin selection, vector competency and other experiments. Each aim dovetails with the cosponsors' research and my long-term career goals. Discoveries from plant- pathogen systems have led directly to a greater understanding of human-pathogen interactions. Conserved defense signaling pathways, innate immunity and many other insights that apply to all host-pathogen interactions began with studies of plants and their pathogens. Understanding the genetic, physiological and evolutionary basis of the SIS response to virulent Ps and herbivory with the goal of understanding pathogenesis and evolution of virulence is therefore directly related to the mission of the NIH.

描述（由申请人提供）：通过使用模型遗传系统，特别是在植物病原体的情况下，已经彻底改变了对传染源引起疾病的机制的理解。进化生物学家还为我们对传染病动态（包括毒力进化）的理解提供了重要的见解。尽管自然界中的宿主同时受到多种病原体和寄生虫的攻击，但分子生物学家很少研究这种相互作用，因为大多数研究都集中在单一病原体上。相反，尽管有机生物学家研究这些相互作用的目的是揭示宿主-寄生虫相互作用的生态和进化的一般原理，但宿主防御反应介导的生物相互作用的潜在遗传或机制基础却很少被表征。因此，公共卫生研究人员与进化生物学家合作，努力更好地理解和控制传染病。该提案提出的实验旨在表征拟南芥、病原体丁香假单胞菌 (Ps) 和昆虫的三向病理系统模型中病原体对两种宿主防御信号操纵的直接（遗传/生理/机械）和最终（进化）机制食草动物。 Ps 操纵防御信号串扰，导致对相同病原体感染的系统诱导易感性 (SIS) 以及对草食动物的抵抗力或易感性 (SIS) 增加。 SIS 至 Ps 是由茉莉酸类似物冠菌素 (COR) 介导的，COR 是由剧毒 Ps 产生的。然而，介导 SIS 至草食动物的信号尚不清楚，并且在这两种情况下，宿主植物中系统信号背后的基因也是未知的。第一个目标是，我将在初步基因表达实验的基础上来描述两种类型 SIS 的潜在途径。第二个目标，我将通过亲缘选择、向量能力等实验来研究这两种类型的SIS是否存在适应性基础。每个目标都与共同发起人的研究和我的长期职业目标相吻合。植物-病原体系统的发现直接导致了对人类-病原体相互作用的更深入的了解。保守的防御信号通路、先天免疫和许多其他适用于所有宿主-病原体相互作用的见解始于对植物及其病原体的研究。因此，了解 SIS 对毒力 Ps 和食草动物的反应的遗传、生理和进化基础，以了解毒力的发病机制和进化为目标，与 NIH 的使命直接相关。