RoL: FELS: EAGER: Disease resistance as a product of synergy between host immunity and the microbiome

现在已经确定，微生物组（与宿主生物体相关的微生物物种群落）可以增加宿主营养物质的获取并预防疾病。即便如此，哪些细菌群落将为其宿主提供积极的结果仍然无法可靠地预测。在很大程度上，这是因为“健康”微生物组的配置似乎是无限的，这使得分析自然模式变得困难。此外，对微生物组功能的理解目前受到宿主-微生物和微生物-微生物相互作用的复杂性的阻碍，这些相互作用是这些积极结果的基础。 然而，尽管存在这种复杂性，但最近的研究表明，微生物组介导的针对病原体建立和疾病的保护的一般原则可能是可识别的。新的测序技术和新的实验系统的开发的结合提供了一个独特的机会，开始解开微生物组和疾病之间的相互作用，并检查微生物组介导的保护跨不同宿主物种的一般性。这样一项工作的起点集中在广泛的宿主范围病原体上，目前存在多个宿主微生物组介导保护的证据。使用两种不同的植物-微生物组-病原体系统（一种与林业管理直接相关，另一种与农业直接相关）作为概念证明，目前的工作旨在建立一个预测框架，用于识别与宿主免疫系统协同作用以抵御疾病的微生物财团。基于现有的数据，从七叶树的出血溃疡病和番茄植物的细菌斑点，这两者都是由病原菌的致病变种，假单胞菌引起的，该项目将测试的想法，有基本的微生物群介导的保护，适用于整个系统的一般规则。在这两个系统中的每一个中，先前的证据已经将叶圈（地上）微生物组的多样性和组成与病原体定殖成功和/或植物疾病结果联系起来。该项目将使用来自自然树系统的非培养物依赖性测序数据，根据微生物组组成、多样性和/或功能，预测微生物组介导的疾病保护。然后，这些预测将使用番茄植物中的合成微生物组进行测试，其中直接（微生物-微生物）和间接（植物介导）影响在形成微生物组介导的保护中的相对贡献可以通过实验进行量化。通过将高通量幼苗引发试验与合成微生物组方法相结合，该项目旨在确定与植物防御协同作用的疾病保护群落特性。该项目试图揭示的微生物组介导的保护的一般原则有可能广泛适用于整个系统，并为人类健康和农业中的保护性微生物群落的预测提供信息。这项工作的最终目标是能够利用这些宿主-微生物组-病原体相互作用来实现强大和持久的疾病保护，其结果将有助于农业和自然系统的管理，该奖项反映了NSF的法定使命，并通过利用基金会的知识价值和更广泛的影响进行评估，被认为值得支持审查标准。

It is now well-established that the microbiome (the community of microbial species associated with a host organism) can increase host nutrient acquisition and protect against disease. Even so, which communities of bacteria will provide positive outcomes for their hosts cannot be reliably predicted. In large part, this is because there are seemingly infinite configurations of "healthy" microbiomes, making analysis of natural patterns difficult. Moreover, understanding of microbiome function is currently hampered by the complexity of host-microbe and microbe-microbe interactions underlying these positive outcomes. Despite this complexity, however, recent research suggests that general principles underlying microbiome-mediated protection against pathogen establishment and disease may be identifiable. The combination of new sequencing technologies and the development of new experimental systems presents a unique opportunity to begin disentangling the interactions between the microbiome and disease, and to examine the generality of microbiome-mediated protection across different host species. A starting point for such an undertaking focuses on a broad host range pathogen, for which evidence of microbiome-mediated protection currently exists across multiple hosts. Using two different plant-microbiome-pathogen systems (one with direct relevance to forestry management and the other to agriculture) as proof of concept, the current work aims to build a predictive framework for identifying microbial consortia that synergize with the host immune system to protect against disease. Building upon existing data from Bleeding Canker disease of Horse Chestnut trees and Bacterial Speck of Tomato plants, both of which are caused by pathovars of the bacterial pathogen, Pseudomonas syringae, this project will test the idea that there are general rules underlying microbiome-mediated protection that are applicable across systems. In each of these two systems, previous evidence has linked the diversity and composition of the phyllosphere (above ground) microbiome to pathogen colonization success and/or plant disease outcome. This project will use culture-independent sequencing data from the natural tree system to generate predictions about microbiome-mediated disease protection based on microbiome composition, diversity, and/or function. These predictions will then be tested using synthetic microbiomes in tomato plants, where the relative contributions of direct (microbe-microbe) and indirect (plant-mediated) effects in shaping microbiome-mediated protection can be experimentally quantified. By combining high-throughput seedling priming assays with a synthetic microbiome approach, the project seeks to identify disease protective community properties that synergize with plant defenses. The general principles of microbiome-mediated protection that this project seeks to uncover have the potential to be broadly applicable across systems, and inform predictions about protective microbial communities in human health and agriculture. The ultimate goal of the work is to be able to leverage these host-microbiome-pathogen interactions to attain robust and durable disease protection, and the results will aid in management of both agricultural and natural systems, and the development of probiotic treatment against plant disease.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.