Collaborative Research: Tradeoffs between specialist and generalist strategies for host immune evasion in a vector-borne bacterium

合作研究：媒介传播细菌宿主免疫逃避的专业策略和通才策略之间的权衡

基本信息

批准号：
1755370
负责人：
Maria Diuk-Wasser
金额：
$ 50.99万
依托单位：
Columbia University
依托单位国家：
美国
项目类别：
Continuing Grant
财政年份：
2018
资助国家：
美国
起止时间：
2018-08-15 至 2022-07-31
项目状态：
已结题

来源：
https://www.nsf.gov/awardsearch/showAward?AWD_ID=1755370&HistoricalAwards=false
关键词：
Collaborative Research Tradeoffs between specialist

项目摘要

This research addresses a unique example of how the environment can impact human and animal health by shaping bacterial communities in nature. Microbes causing human or animal disease differ in the number of hosts they can infect; while some specialize on a single animal/plant, others are able to infect a wide range. Specialist organisms may be better able to escape the host immune system and thus survive, but they risk becoming extinct if the host becomes rare. Pathogens with wide host ranges are often better able to 'jump' to new hosts, driving epidemics. This award will investigate how Borrelia burgdorferi - the bacterium that causes Lyme disease - escapes killing by the immune system of its natural host and whether different genetic types of this bacterium are uniquely adapted to mammals versus birds in nature. This award will also investigate whether Borrelia diversity is explained by adaptation to different hosts or, alternatively, by the targeting of the most common strains by host antibodies, allowing coexistence of rarer strains. Borrelia diversity directly impacts human health because strains cause differential disease severity. This award will increase knowledge about how ecology and evolution of microbes impacts human health. It will develop educational materials and expand outreach into communities about the links between the environment and human health. In addition, it will provide extensive and interdisciplinary training, at all educational levels, in the fields of disease ecology, molecular ecology and eco-epidemiology.This award will determine the extent of specialization and immune-mediated competition among strains of B. burgdorferi in different ecological contexts and test the hypothesis that these phenotypic traits are important drivers of B. burgdorferi diversity, community structure and host specialization evolution. While there is evidence of differential B. burgdorferi host association which could drive genetic polymorphisms ('multiple niche polymorphism'), other studies claim that immune-mediated balancing selection acting on one or more B. burgdorferi outer surface proteins can maintain the observed polymorphisms without invoking directional processes ('negative frequency-dependent selection'). This award will disentangle the contribution of multiple mechanisms to B. burgdorferi diversity by assessing strain prevalence in multiple host species by applying deep amplicon sequencing to data from a 6-year-long study in a simplified host community. The physiological basis of host specificity will be explored by evaluating in vitro survival of B. burgdorferi strains when exposed to immune components in serum of different local hosts. Host-specificity related fitness and immune-mediated competition between strains will be assessed with in vivo transmission experiments. The processes by which host specialization and immune-mediated competition determine strain diversity and evolution in different ecological contexts will be examined using novel mathematical models. This study will provide strong evidence of the nature of B. burgdorferi adaptations to avoid the immune system of its natural hosts. It will determine whether these adaptations are species-specific and identify the consequences of host specificity on the structure and diversity of B. burgdorferi strain community. The award will provide multi-disciplinary training to graduate students, including under-represented minorities, and postdoctoral fellows in disease ecology and modeling. To broaden the impact of the work, researchers will leverage contacts with local environmental groups to conduct outreach within the local community.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.

这项研究讲述了环境如何通过塑造自然界细菌群落来影响人类和动物健康的独特例子。引起人类或动物疾病的微生物在他们可能感染的宿主数量上有所不同。虽然有些专门研究单个动物/植物，但有些人能够感染广泛的范围。专业生物可能会更好地逃脱宿主免疫系统并因此生存，但是如果宿主很少见，它们就会灭绝。带有宽敞宿主范围的病原体通常可以更好地“跳入”新宿主，驱动流行病。该奖项将调查伯氏伯氏菌（Borlelia burgdorferi）是如何通过其自然宿主的免疫系统杀死的杀死莱姆病的细菌，以及这种细菌的不同遗传类型是否独特地适合于自然界中的哺乳动物与鸟类。该奖项还将调查是否通过适应不同宿主的适应性或通过宿主抗体将最常见的菌株靶向来解释疏渗道的多样性，从而使稀有菌株共存。伯氏多样性直接影响人类健康，因为菌株会导致疾病差异。该奖项将增加有关微生物的生态和进化如何影响人类健康的知识。它将开发教育材料，并扩大有关环境与人类健康之间联系的社区。 In addition, it will provide extensive and interdisciplinary training, at all educational levels, in the fields of disease ecology, molecular ecology and eco-epidemiology.This award will determine the extent of specialization and immune-mediated competition among strains of B. burgdorferi in different ecological contexts and test the hypothesis that these phenotypic traits are important drivers of B. burgdorferi diversity, community structure and host specialization 进化。虽然有差异性B. burgdorferi宿主协会的证据可以驱动遗传多态性（“多种构矿多态性”），但其他研究声称，免疫介导的平衡选择作用于一个或多个B. burgdorferi外表面蛋白可以维持观察到的多态性的多态性，而无需调用否定的频率依赖性依赖性频率依赖于'）。该奖项将通过评估多种宿主物种的菌株流行率，通过在简化的宿主社区中进行长达6年的研究中的数据来评估多种机制对B. burgdorferi多样性的贡献。当暴露于不同局部宿主的血清中的免疫成分时，将通过评估B. burgdorferi菌株的体外存活来探索宿主特异性的生理基础。宿主特异性相关的适应性和免疫介导的菌株之间的竞争将通过体内传播实验进行评估。主机专业化和免疫介导的竞争决定了在不同生态环境下的应变多样性和进化的过程，将使用新颖的数学模型进行检查。这项研究将提供有力的证据，表明伯格多尔河芽孢杆菌适应性的性质，以避免其自然宿主的免疫系统。它将确定这些适应是否是特定物种的，并确定宿主特异性对B. burgdorferi菌株社区的结构和多样性的后果。该奖项将向研究生（包括代表性不足的少数民族以及疾病生态学和建模的博士后研究员）提供多学科培训。为了扩大作品的影响，研究人员将利用与当地环境团体的联系来进行当地社区内的宣传。该奖项反映了NSF的法定任务，并被认为是值得通过基金会的知识分子优点和更广泛影响的评估评估标准通过评估来支持的。

项目成果

期刊论文数量（8）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Host adaptation drives genetic diversity in a vector-borne disease system.

DOI：
10.1093/pnasnexus/pgad234
发表时间：
2023-08
期刊：
PNAS NEXUS
影响因子：
0
作者：
Combs, Matthew A.;Tufts, Danielle M.;Adams, Ben;Lin, Yi-Pin;Kolokotronis, Sergios-Orestis;Diuk-Wasser, Maria A.
通讯作者：
Diuk-Wasser, Maria A.

Outer surface protein polymorphisms linked to host‐spirochete association in Lyme borreliae

外表面蛋白多态性与莱姆疏螺旋体宿主螺旋体关联相关

DOI：
10.1111/mmi.14209
发表时间：
2019
期刊：
Molecular Microbiology
影响因子：
3.6
作者：
Tufts, Danielle M.;Hart, Thomas M.;Chen, Grace F.;Kolokotronis, Sergios‐Orestis;Diuk‐Wasser, Maria A.;Lin, Yi‐Pin
通讯作者：
Lin, Yi‐Pin

Cellular and immunological mechanisms influence host-adapted phenotypes in a vector-borne microparasite