Transovarial transmission of yersinia pestis in fleas

项目总结 跳蚤传播人类疾病在世界各地都有发生，其中最引人注目的是 黑死病由鼠疫耶尔森氏菌引起的腺鼠疫或黑死病虽然不是曾经的大流行，但瘟疫 继续在四大洲造成每年的人类死亡，包括北美，在那里它是地方性的 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。 每年在草原上大量分布的草原土拨鼠种群中。 由于它作为生态系统工程师的角色，以及与濒危的黑脚雪貂的营养关系，在那里 对土拨鼠的大量监测数据记录了由流行性出血热暴发引起的广泛死亡 瘟疫。这些疫情定期发生，尽管不一定每年在特定地区发生，而且可以大量 影响当地生态系统。一些地理区域经历了地方性鼠疫，其特点是 在动物疫病发生之间，野生动物很少或根本没有鼠疫活动的时期。虽然有100多个 多年来关于跳蚤传播鼠疫的研究，对地方病的认识仍然存在重大差距 尽管这一循环是鼠疫在全球持续存在及其对公共卫生的持续威胁的基础。 本申请中提出的研究涉及影响地方病循环的关键因素。具体来说， 这项研究将集中于重新定义鼠疫杆菌的经卵传播作为过程的驱动力的作用。 瘟疫循环。拟议的项目建立在强有力的初步数据的基础上，这些数据记录了经卵传播的猪瘟 实验室饲养和感染印鼠客蚤的鼠疫耶尔森氏菌。这些数据表明，细菌是 通过这种机制传播的病毒可以在所有发育阶段存活，甚至在这些环境中生长， 这可能表明，在没有鼠疫的情况下，经卵巢传播可能会影响鼠疫的持久性。 广泛传播的哺乳动物疾病。拟议的工作将对这些观察结果采取后续行动， 结合高分辨率电子显微镜检查细菌的最先进方法 中肠上皮内的相互作用，以确定可能用于扩散的机制 从消化道到跳蚤的生殖器官。此外，对每一株鼠疫杆菌的成像 系列块面扫描电子显微镜的使用将促进发展阶段 VolumeScope(SBF-SEM)重建高分辨率3D图像，说明 支持鼠疫杆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具有重要意义。这种高风险、高回报的结果 R21项目将为长期、跨学科的机制和生态研究奠定基础 鼠疫杆菌在跳蚤中的经卵传播将有助于我们了解鼠疫对人类的风险 还有动物。

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.