Vector and Host Contributions to the Regulation of E. chaffeensis Gene Expression

项目摘要 由埃立克体属和无形体属立克次体引起的疾病日益引起人类健康问题 近年来，它是美国和世界许多地区蜱传感染的第二大原因。 世界它们包括由查菲埃里希体引起的人单核细胞埃里希体病。尽管有复杂的 在脊椎动物和蜱宿主的防御系统中，立克次体逃避宿主的清除。E.查菲因 巨噬细胞和蜱细胞在几种外膜蛋白和效应物的表达上存在显著差异， 通过其分泌途径分泌的蛋白质。研究结果表明，不同的蜱类和脊椎动物 宿主细胞特异性表达导致宿主应答的变化和宿主中清除的延迟。的 先前资助的项目的中心假设是E. Chaffeensis差异调节基因 宿主特异性基因表达对其在脊椎动物和蜱细胞中的存活至关重要。 上一个供资周期的进展构成了本次延期申请的坚实基础， 继续测试上述创新假设。本申请的具体目的是1）表征 E. chaffeensis RNA聚合酶复合物支持理解载体和脊椎动物宿主特异性 2）评价宿主特异性差异表达的意义 表达的特征突变的三个基因被确定为必要的E. chaffeensis体内生长， 3）进行突变分析和体内筛选以鉴定E.恰菲 发病机制

PROJECT SUMMARY Illnesses caused by rickettsiales of the genera Ehrlichia and Anaplasma are a growing human health concern in recent years and are the second leading cause of tick-borne infections in the USA and many parts of the world. They include human monocytic ehrlichiosis caused by Ehrlichia chaffeensis. Despite the sophisticated systems of defense in vertebrate and tick hosts, the rickettsiales evade the host clearance. E. chaffeensis in macrophages and tick cells differ significantly in expression of several outer membrane proteins and effector proteins secreted via its secretary pathways. Research results demonstrate that differential tick and vertebrate host cell-specific expression contributes to the varied host response and delayed clearance in a host. The central hypothesis of the previously funded project is that E. chaffeensis differentially regulates gene expression and that the host-specific gene expression is essential for its survival in vertebrate and tick cells. Progress from the previous funding cycle forms the strong foundation for this renewal application and to continue testing the above stated innovative hypothesis. Specific aims of this application are 1) to characterize E. chaffeensis RNA polymerase complex in support of understanding how vector and vertebrate host-specific differential gene expression is accomplished, 2) to evaluate the significance of host-specific differential expression by characterizing mutations in three genes identified as essential for E. chaffeensis in vivo growth, and 3) to perform mutational analysis and in vivo screening to identify genes essential for the E. chaffeensis pathogenesis.