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

• 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

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.

这项研究提出了一个独特的例子，说明环境如何通过塑造自然界中的细菌群落来影响人类和动物的健康。导致人类或动物疾病的微生物在它们可以感染的宿主数量上有所不同;虽然有些专门针对单一动物/植物，但其他微生物能够感染广泛的宿主。专业生物可能更能逃脱宿主的免疫系统，从而生存下来，但如果宿主变得稀少，它们就有灭绝的危险。具有广泛宿主范围的病原体通常能够更好地“跳跃”到新宿主，从而推动流行病。该奖项将研究导致莱姆病的伯氏疏螺旋体如何逃脱其天然宿主免疫系统的杀死，以及这种细菌的不同遗传类型是否独特地适应自然界中的哺乳动物和鸟类。该奖项还将调查疏螺旋体的多样性是否可以通过适应不同的宿主来解释，或者通过宿主抗体靶向最常见的菌株来解释，从而允许罕见菌株共存。疏螺旋体的多样性直接影响人类健康，因为菌株导致不同的疾病严重程度。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。 它将编制教育材料，并将环境与人类健康之间的联系扩大到社区。此外，它还将在疾病生态学、分子生态学和生态流行病学领域为各级教育提供广泛的跨学科培训，该奖项将确定B菌株之间的专业化程度和免疫介导的竞争。burgdorferi在不同的生态环境和测试的假设，这些表型性状是B的重要驱动程序。burgdorferi多样性、群落结构和寄主专化性演化。虽然有差异B的证据。除了可以驱动遗传多态性（“多小生境多态性”）的伯氏宿主关联之外，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而不引起定向过程（“负频率依赖性选择”）。该奖项将解开多种机制对B的贡献。通过将深度扩增子测序应用于在简化的宿主群落中进行的长达6年的研究的数据，评估多个宿主物种中的菌株流行率，从而评估burgdorferi多样性。通过评价B的体外存活，将探索宿主特异性的生理基础。不同宿主血清中的免疫成分。将通过体内传播实验评估菌株之间的宿主特异性相关适应性和免疫介导的竞争。宿主专业化和免疫介导的竞争决定菌株的多样性和进化在不同的生态环境中的过程将使用新的数学模型进行研究。这项研究将为B的性质提供强有力的证据。burgdorferi适应以避开其天然宿主的免疫系统。它将确定这些适应是否是物种特异性的，并确定宿主特异性对B结构和多样性的影响。burgdorferi菌株群落该奖项将为研究生提供多学科培训，包括代表性不足的少数民族，以及疾病生态学和建模方面的博士后研究员。为了扩大工作的影响，研究人员将利用与当地环保团体的联系，在当地社区开展外联活动。该奖项反映了NSF的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

项目成果

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
• 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

• DOI: 10.1098/rspb.2021.2087
• 发表时间: 2022-02-23
• 期刊: PROCEEDINGS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES
• 影响因子: 4.7
• 作者: Lin, Yi-Pin;Tufts, Danielle M.;Diuk-Wasser, Maria A.
• 通讯作者: Diuk-Wasser, Maria A.