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）：了解传染剂引起疾病的机制已通过使用模型遗传系统彻底改变了疾病，尤其是在植物病原体的情况下。进化生物学家还为我们对感染性疾病动态的理解（包括毒力的进化）提供了重大见解。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，但这种相互作用很少被分子生物学家研究，因为大多数研究都集中在单个病原体上。相反，尽管有机生物学家研究了这些相互作用的目的是揭示宿主 - 寄生虫相互作用的生态学和演变的一般原则，但很少表征由宿主防御反应介导的生物相互作用的基本遗传或机械基础。因此，公共卫生研究人员已经与进化生物学家一起，以更好地理解和控制传染病。该提案提出了旨在表征近端（遗传/生理/机理）和最终（进化）机制的实验，这些机制是两种类型的宿主防御信号传导操纵在涉及拟南芥模型的病原体中，涉及病原体的病原体，病原体（病原体）pseudomonas syringaas（PS）和昆虫疱疹。 PS操纵防御信号交叉讲座，从而导致系统性诱导的易感性（SIS）受到相同病原体感染的感染，并增加了对草食性的耐药性或易感性（SIS）。 SIS至PS是由茉莉酸模拟冠状动脉（COR）介导的，该茉莉酸冠状动脉（COR）由毒性PS产生。但是，介导SIS的信号尚不清楚，在这两种情况下，宿主植物中的系统信号的基因尚不清楚。在第一个目标中，我将基于初步基因表达实验来表征两种类型的SI的途径。在第二个目标中，我将通过进行亲属选择，向量能力和其他实验来调查这两种类型的SIS。每个目标都与共同提案者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人们对人类病原体相互作用有了更大的了解。保守的防御信号通路，先天免疫力以及适用于所有宿主病原体相互作用的许多其他见解始于对植物及其病原体的研究。因此，了解SIS对毒性PS和草食性的反应的遗传，生理和进化基础，目的是了解毒力的发病机理和进化与NIH的使命直接相关。