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.

伯氏疏螺旋体 (Bb) 通过黑腿蜱 (肩胛硬蜱) 传播，作为北美最流行的媒介传播疾病莱姆病 (LD) 的病原体，其公共卫生重要性与日俱增，莱姆病 (LD) 的发病率持续增加。尽管 Bb 通常被认为是地方性动物传播周期 (ETC) 中的病原体，但没有证据表明 Bb 会在其循环的储存宿主或蜱宿主中引发疾病。在这里，我们将肩胛蜱中的 Bb 感染概念化为一种兼性共生，受到蜱内微生物动态以及蜱与构成 ETC 的脊椎动物宿主之间更广泛的生态相互作用的影响。肩胛硬蜱是研究生态相互作用网络的一个有价值的候选者，因为它的微生物组涵盖了微生物与节肢动物宿主相互作用的一系列关系，从短暂的共生环境获得微生物到可遗传的专性细胞内内共生体，其中最主要的是布氏立克次体（Rb）。拟议的研究重点关注假设影响 Bb-ETC 的相互作用，将描述蜱中 Bb 定植的特征，评估 Bb 丰度和基因表达的变化，作为假定的营养内共生体 Rb 和蜱微生物组的存在的函数，其特征在于 1) 细菌分类群 (16S 核糖体 RNA) 的相对丰度和 2) 操纵的分类微生物组 组合（即自然田间收集的蜱虫；人工实验室饲养；以及在无菌容器中饲养的破坏实验室（SA1）。将测量 Bb 对蜱虫生活史特征、生存、代谢和行为以及相关基因表达（Bb 和蜱虫）的影响，估计 Bb-蜱虫关联的效益/成本，并测试潜在机制（SA2）。最后， 将使用两个建模框架对 Bb-ETC 的蜱内、蜱微生物和蜱微生物相互作用（Bb-Rb 相互作用和分类组合）进行估计和评估。基于代理的模型将重点关注微生物介导的蜱血粉充血、发育、生存、行为和繁殖力方面的差异（SA3.1）。 Bb-ETC 动力学的隔室模型 更广泛的时间尺度还将考虑多个周期的季节性。与现场和实验室实验以及经验数据并行开发并提供信息的模型将用于开发正式的蜱矢量容量定义，其中包括蜱微生物组的重要组成部分和影响（SA3.2）。这些结果将用于增进对 Bb-ETC 的理解和 LD 风险指标的预测。