Transovarial transmission of yersinia pestis in fleas

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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.