Resistance Variation to Endemic Disease as a Risk Factor to New Disease Emergence

人类活动和环境变化正以前所未有的速度重新分布物种，新的寄主-病原体组合已经成为对人类、作物和自然生态系统的主要威胁。因此，外来病原体传入时影响疾病传播的因素对于改进疾病出现的风险评估至关重要。尽管寄主个体之间的抗病变异被认为是物种内流行病学动态的一个关键因素，但在新引入的疾病背景下，站立变异在抗病中的作用几乎没有得到考虑。事实上，植物和动物物种对病原体表现出巨大的抵抗力变化，这是一个物种在自然界中通常不会遇到的。一项研究还发现，耐药机制往往会在不同类型的病原体之间产生相关的结果，无论是积极的还是消极的。这些结果表明，对地方性疾病的抗性机制表现出的特性可能是对外来病原体反应的重要差异的基础，因此它们建立的可能性也是如此。易于处理的植物-真菌模型的初步结果支持这一可能性，该项目将结合田间和温室工作，以及理论的发展，建立一个预测框架，预测新疾病传播到对地方性病原体抵抗力不同的种群的可能性。智力价值：拟议的调查涉及两名PI以及一个理论和实地研究合作团队，将在与日益频繁的病原体和宿主引入所造成的日益严重的全球威胁相关的疾病传播领域开辟新的天地。该项目旨在揭示疾病在新的宿主-病原体组合中传播的基本原理，这些组合可能源于对不同病原体的抗病能力的相关变异。此外，这些研究还可以扩展到改善对多种地方病之间的相互作用和宿主-病原体系统中的生态进化反馈的预测。这项工作对病原体多样化这一密切相关的领域具有强烈的影响，以及根本性不同的遗传过程是否构成了宿主抵抗广泛病原体与狭义病原体的能力的基础。对引入的病原体的抗性变异对于理解在自然界中观察到的宿主-病原体亲和力的多样性是核心的，对于更好地理解人类、农业和野生种群中新出现的疾病的风险是关键的。

Human activities and environmental change are redistributing species at an unprecedented rate, and new host-pathogen combinations have become a major threat to humans, crops, and natural ecosystems. Therefore, the factors affecting disease transmission upon introduction of a foreign pathogen are critically important to improving risk assessment for disease emergence. Although variation among host individuals in disease resistance is regarded as a key factor in epidemiological dynamics within species, the role of standing variation in resistance has received little consideration in the context of newly introduced disease. In fact, plant and animal species show substantial resistance variation to pathogens that a species does not normally encounter in nature. One also finds that resistance mechanism can often have correlated outcomes, either positively or negatively, across different pathogen types. These results suggest that resistance mechanisms to endemic diseases exhibit properties that may underlie the important variation in responses to foreign pathogens and therefore the likelihood of their establishment. Initial results with a tractable plant-fungus model support this possibility, and this project will undertake a combination of field and greenhouse work, together with the development of theory, to build a predictive framework for the likelihood of new disease transmission into a population varying in resistance to its endemic pathogens. Intellectual Merit: The proposed investigations, involving two PIs, and a collaborating team on theory and field studies, will break new ground in the area of disease transmission related to the mounting global threats from increasingly frequent pathogen and host introductions. The project aims to reveal fundamental principles for disease spread in new host-pathogen combinations that may stem from correlated variation in disease resistance to different pathogens. Furthermore, the studies can be extended to improve predictions on the interactions of multiple endemic diseases and of eco-evolutionary feedbacks in host-pathogen systems. The work has strong implications to the closely allied field of pathogen diversification and whether fundamentally different genetic processes underlie a host's ability to resist a broad vs. a narrow range of pathogens. The role of resistance variation to introduced pathogens is central to understanding the diversity of host-pathogen affinities observed in nature, and central to developing better understanding of risks from emerging diseases in human, agricultural and wild populations.