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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.

项目摘要跳蚤传播人类疾病在世界各地都有发生，其中最值得注意的是黑死病，由鼠疫耶尔森氏菌引起。虽然不是流行病，它曾经是，鼠疫在四大洲，包括流行于北美的疟疾，每年仍造成人类死亡在美国西部农村的啮齿动物种群中。在这个地区，跳蚤传播鼠疫草原土拨鼠数量庞大，遍布整个草原。由于其作为生态系统工程师的作用以及与濒危黑脚雪貂的营养关系，对草原土拨鼠的充分监测数据记录了由流行性疾病爆发引起的广泛死亡，瘟疫这些疾病的爆发是有规律的，虽然不一定每年都在某一地区发生，影响当地生态系统。一些地理区域经历了地方性鼠疫，其特征是长期的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多个经过多年对鼠疫跳蚤传播的研究，对地方病的了解仍存在重大差距尽管这种循环是鼠疫全球持续存在及其对公共卫生持续威胁的基础，但它仍然是一个恶性循环。本申请中提出的研究解决了影响地方病周期的关键因素。具体地说，这项研究将集中于重新定义Y染色体跨卵传播的作用。鼠疫作为森林的驱动力瘟疫循环拟议的项目是建立在强有力的初步数据记录跨卵巢传播 Y.来自实验室饲养和感染的印鼠客蚤的鼠疫。这些数据表明，通过这种机制传播的病毒在所有发育阶段都能存活，甚至在这些环境中生长，这可能表明，在缺乏免疫力的情况下，经卵巢传播可能会影响鼠疫的持续性。广泛传播的哺乳动物疾病。拟议的工作将对这些意见采取后续行动，最先进的方法，结合高分辨率透射电子显微镜检查细菌中肠上皮内的相互作用，以确定可能用于传播的机制从跳蚤的消化道到生殖器官此外，Y.每个人身上都有鼠疫开发阶段将通过使用连续块面扫描电子显微镜来促进容积镜（SBF-SEM）重建高分辨率3D图像，显示解剖特征，支持Y。鼠疫菌在各个生命阶段的生存和生长。拟议的工作将严格解决潜在的这一机制对鼠疫的进化和持久性的重要性。这种高风险、高回报的 R21项目将为长期的、跨学科的机制和生态学研究奠定基础。 Y.经卵巢传播跳蚤中的鼠疫，这将有助于我们了解鼠疫对人类的风险和动物