Transovarial transmission of yersinia pestis in fleas

跳蚤中鼠疫耶尔森氏菌的跨卵巢传播

基本信息

批准号：
10727534
负责人：
DEBORAH M ANDERSON
金额：
$ 18.7万
依托单位：
UNIVERSITY OF MISSOURI-COLUMBIA
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-06-01 至 2025-05-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10727534
关键词：
Address Adherence Adult Adverse effects Anatomy Animals Area Bacteria Biological Assay Blood Bubonic Plague Contracts Data Development Disease Disease Outbreaks Ecology Ecosystem Electron Microscopy Engineering Environment Epithelial Cells Epithelium Event Evolution Face Ferrets Fleas Foundations Gastrointestinal tract structure Generations Geographic Locations Goals Grasslands Growth Human Image Immunity Infection Knowledge Laboratories Larva Life Life Cycle Stages Maintenance Mammals Mediating Microbial Biofilms Microscopic Midgut Modernization Montana North America Outcome Pathogenesis Persons Plague Play Population Prairie Dog Precipitation Production Proteins Proventriculus Public Health Pupa Rattus Reporter Research Resolution Risk Rodent Role Rural Population Scanning Electron Microscopy Technology Temperature Three-Dimensional Image Tissues Transmission Electron Microscopy United States Virulent Visualization Wild Animals Work Yersinia pestis Zoonoses egg enzootic epizootic experience experimental study feeding flea-borne follow-up foot high reward high risk human disease human mortality innovation mathematical model mortality mouse model next generation pandemic disease reproductive organ surveillance data transmission process vector

项目摘要

PROJECT SUMMARY Flea transmission of human diseases has occurred throughout the world, the most notable of which is the bubonic plague or black death, caused by Yersinia pestis. Although not the pandemic it once was, plague continues to cause annual human mortality across four continents, including North America, where it is endemic in the rodent populations of the rural western United States. In this region, flea transmission of plague occurs annually among the large prairie dog populations which are abundantly distributed throughout the grasslands. Due to its role as an ecosystem engineer and trophic relationship with the endangered black-footed ferret, there is ample surveillance data on prairie dogs documenting widespread mortality caused by epizootic outbreaks of plague. These outbreaks occur regularly, though not necessarily annually in a given area, and can substantially impact the local ecosystem. Some geographic areas experience enzootic plague, characterized by prolonged periods with little to no plague activity in wildlife in between epizootic events. Although there is more than 100 years of research on flea transmission of plague, there remain significant gaps in understanding the enzootic cycle, even though this cycle underlies the global persistence of plague and its continued threat to public health. The research proposed in this application addresses key factors that influence the enzootic cycle. Specifically, the research will focus on redefining the role of transovarial transmission of Y. pestis as a driver of the sylvatic plague cycle. The proposed project is built on strong preliminary data documenting transovarial transmission of Y. pestis from laboratory-reared and infected Xenopsylla cheopis. These data suggest that bacteria that are transmitted via this mechanism survive through all developmental stages and even grow in these environments, which may indicate that transovarial transmission could impact the persistence of plague in the absence of widespread mammalian disease. The proposed work will follow-up on these observations with an innovative, state-of-the-art approach that incorporates high resolution transmission electron microscopy to examine bacterial interactions within the midgut epithelium in order to identify the mechanism that may be used for dissemination from the digestive tract to the reproductive organs of the flea. Furthermore, imaging of Y. pestis in each developmental stage will be facilitated by the use of the Serial Block-Face Scanning Electron Microscopy Volumescope (SBF-SEM) to reconstruct a high-resolution 3D image that illustrates the anatomical features that support Y. pestis survival and growth in each life stage. The proposed work will rigorously address the potential importance of this mechanism to the evolution and persistence of plague. Results of this high-risk, high-reward R21 project will lay the groundwork for long term, inter-disciplinary mechanistic and ecological studies of transovarial transmission of Y. pestis in fleas that will help inform our understanding of plague risk for humans and animals.

项目概要跳蚤传播人类疾病的情况在世界各地都有发生，其中最引人注目的是腺鼠疫或黑死病，由鼠疫耶尔森氏菌引起。虽然不是以前那样的大流行病，但瘟疫每年继续导致四大洲人类死亡，其中包括流行的北美美国西部农村的啮齿动物种群。该地区发生跳蚤传播鼠疫的情况每年都有大量的草原土拨鼠种群分布在整个草原上。由于其作为生态系统工程师的作用以及与濒临灭绝的黑脚雪貂的营养关系，是否有足够的关于草原土拨鼠的监测数据记录了因动物流行病爆发而造成的广泛死亡瘟疫。这些爆发定期发生，但不一定每年在特定地区发生，并且可能会严重影响影响当地的生态系统。一些地理区域遭受地方性鼠疫，其特点是长期在动物流行病事件之间，野生动物很少或没有鼠疫活动的时期。虽然有100多个尽管对跳蚤传播鼠疫的研究已有多年，但在了解地方性动物病方面仍存在重大差距循环，尽管这种循环是鼠疫在全球持续存在及其对公众健康持续威胁的基础。本申请提出的研究解决了影响地方性动物流行周期的关键因素。具体来说，该研究将侧重于重新定义鼠疫耶尔森氏菌经卵巢传播作为森林化驱动因素的作用瘟疫循环。拟议的项目建立在记录跨卵巢传播的强有力的初步数据的基础上来自实验室饲养并感染的印鼠客鼠疫杆菌。这些数据表明，细菌通过这种机制传播的病毒可以在所有发育阶段存活下来，甚至可以在这些环境中生长，这可能表明，在没有病毒的情况下，经卵巢传播可能会影响鼠疫的持续存在。广泛的哺乳动物疾病。拟议的工作将以创新的、最先进的方法，结合高分辨率透射电子显微镜来检查细菌中肠上皮内的相互作用，以确定可用于传播的机制从跳蚤的消化道到生殖器官。此外，每个鼠疫耶尔森氏菌的成像使用串行块面扫描电子显微镜将促进开发阶段 Volumescope (SBF-SEM) 可重建高分辨率 3D 图像，说明解剖学特征支持鼠疫耶尔森氏菌在每个生命阶段的存活和生长。拟议的工作将严格解决潜在的问题这种机制对鼠疫的进化和持续存在的重要性。这种高风险、高回报的结果 R21项目将为长期、跨学科机制和生态学研究奠定基础跳蚤中鼠疫耶尔森氏菌的跨卵巢传播将有助于我们了解人类鼠疫风险和动物。