Investigations of Lyme spirochete transmission as a complex network of microbial and ecological interactions

莱姆螺旋体传播作为微生物和生态相互作用的复杂网络的研究

• 批准号: 10596793
• 负责人: Jannelle Couret
• 金额: $ 57.27万
• 依托单位: UNIVERSITY OF RHODE ISLAND
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-16 至 2026-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10596793
• 关键词: Arthropods; Behavior; Black-legged Tick; Borrelia burgdorferi; Categories; Complex; Costs and Benefits; Data; Development; Disease; Disease model; Etiology; Fertility; Foundations; Future; Gene Expression; Heritability; Incidence; Infection; Investigation; Lyme Disease; Measures; Mediating; Metabolism; Microbe; Modeling; North America; Nutritional; Public Health; RNA, Ribosomal, 16S; Rickettsia; Sterility; Testing; Tick-Borne Diseases; Ticks; Time; Vector-transmitted infectious disease; Vectorial capacity; Work; base; disorder risk; endosymbiont; enzootic; improved; laboratory experiment; life history; microbial; microbiome; mutualism; pathogen; tick feeding; trait; transmission process; vector tick

Borrelia burgdorferi (Bb), transmitted via the blacklegged tick (Ixodes scapularis), is of growing public health importance as the etiologic agent of the most prevalent vector-borne disease in North America, Lyme disease (LD), which continues to increase in incidence. Although often framed as a pathogen in the Enzootic Transmission Cycle (ETC), there is no evidence that Bb elicits disease in either the reservoir or tick hosts between which it cycles. Here, we conceptualize Bb-infection in I. scapularis ticks as a facultative mutualism that is influenced by microbial dynamics within ticks and the broader context of ecological interactions between ticks and vertebrate hosts comprising the ETC. Ixodes scapularis is a valuable candidate to study networks of ecological interactions, as its microbiome encompasses the spectrum of relationships in which microbes can engage with arthropod hosts from transitory, commensal environmentally-acquired microbes to heritable obligate, intracellular endosymbionts, the most predominant of which is Rickettsia buchneri (Rb). Focusing on interactions hypothesized to influence the Bb-ETC, the proposed study will characterize Bb colonization in ticks, evaluating changes in Bb abundance and gene expression as a function of the presence of the putative nutritional endosymbiont Rb and the tick microbiome as characterized by 1) the relative abundance of bacterial taxa (16S ribosomal RNA) and 2) manipulated, categorical microbiome assemblages (i.e., natural-field collected ticks; artificial-lab reared; and disrupted-lab reared in sterile-containers (SA1). Bb effects on tick life-history traits, survival, metabolism and behavior and associated gene expression (of Bb and tick) will be measured, estimating the benefits/costs of Bb-tick associations, and testing potential mechanisms (SA2). Finally, the cumulative impacts of within-ticks, tick-microbe, and tick-microbiome interactions (Bb-Rb interactions and categorical assemblages) will be estimated and evaluated for the Bb-ETC using two modeling frameworks. An agent based model will focus on microbe-mediated differences in tick bloodmeal engorgement, development, survival, behavior, and fecundity (SA3.1). A compartmental model of Bb-ETC dynamics over a broader time scale will also consider seasonality across multiple cycles. Models, developed in parallel with and informed by field and lab experiments and empirical data will be leveraged to develop a formal tick vectorial capacity definition inclusive of important components and effects of the tick microbiome (SA3.2). These results then will be leveraged to improve understanding of Bb-ETC and prediction of LD risk indicators.

通过Blacklegged Tick（Ixodes scapularis）传播的Borrelia burgdorferi（BB），作为北美最普遍的载体传播疾病的病因学药物，莱姆病（LD）的病因学代理人越来越重要。尽管在Enzootic传播周期（ETC）中通常是病原体，但没有证据表明BB在其循环之间引起了储层或tick宿主的疾病。在这里，我们将I. capularis tick的BB感染概念化为一种辅助互助，受tick中的微生物动力学的影响以及tick虫和脊椎动物之间的生态相互作用的更广泛的背景。 ixodes肩cap是研究生态相互作用网络的重要候选者，因为其微生物组包含了一系列关系，其中微生物可以与临时，环境可观的微生物与可遗传的义务，可遗传性的，内细胞内的内膜内膜内膜内部的节肢动物宿主互动，最重要的是buchiabikiabikiabikiabikia buchiabikiabikia beceia bece ai bece ai bece bee bee bee bee bee bee bee bee bee bee bee bee bee bee bee bee bee bee bee bee bee bee bee bee bee bee）拟议的研究专注于假设的相互作用，拟议的研究将表征tick中的BB定殖，评估BB丰度的变化和基因表达的变化，这是假定的营养内共生体内rb的存在的函数，以及tick小滴答物的tick虫，是由16s rib属于rib rib subs的特征（1）级别的rib序列。组合（即，自然田收集的壁虱；饲养的人造lab；在无菌容器中饲养的破坏性LAB（SA1）（SA1）。BB对tick虫的生命历史特征，生存，代谢和相关的基因表达（BB和BB的基因表达（BB和BB）的影响（BB和tick tick的tick tick tick）的效果，并将估算到BB-TICK的收益/测试（BB）的收益/测试（bb）的成本（最终）。将使用两个基于代理的模型对BB-ETC进行挑战，并评估BB-ETC的挑战，tick-microbe和Tick-Microbiome相互作用（BB-RB相互作用和分类组合）。 BB-ETC动力学在更广泛的时间尺度上的隔室模型也将考虑多个周期的季节性。将利用与现场和实验室实验以及经验数据同时开发的模型，以开发正式的tick式矢量容量定义，其中包括重要组成部分以及tick微生物组的效果（SA3.2）。然后将利用这些结果来提高对BB-ETC的了解和LD风险指标的预测。