Anaplasma phagocytophilum induce Ixodes scapularis antifreeze glycoprotein gene e

描述（由申请方提供）：肩突硬蜱在美国东北部和上中西部地区越冬，并传播各种人类病原体，包括人类无形体病病原体嗜吞噬细胞无形体。我的初步数据表明，A.蜱中的嗜吞噬细胞菌增加了I.肩胛肌才能在寒冷中生存我发现了一个I。我们发现了肩胛蜱抗冻糖蛋白，命名为IAFGP，并通过RNAi敲除研究证明了IAFGP对蜱在冷冻环境中存活的重要性。转染研究还表明，IAFGP增加了酵母细胞在低温下的生存力。值得注意的是，我发现A.嗜吞噬细胞菌诱导Iafgp的表达，从而提高了I.肩胛肌这些数据为A.嗜吞噬细胞菌和I.肩胛肌研究了A.嗜吞噬细胞菌诱导IAFgp表达的机制尚不清楚。因此，将进行研究以阐明A.嗜吞噬细胞菌影响载体基因表达，以利于其自身以及其载体宿主在冷冻温度下的存活。以下是具体的目标，将致力于了解机制：在目的1，我将确定和表征iafgp启动子在I。肩胛肌本研究将探讨iafgp启动子在A.嗜吞噬细胞菌感染在目标2中，将进行研究以表征可能参与iafgp启动子诱导的宿主转录激活因子的作用。这些研究不仅阐明了A.嗜吞噬细胞菌和I.肩胛蜱，但也描绘了一个新的方法来研究宿主-病原体相互作用。 公共卫生相关性：在美国，传播多种人类病原体的肩突硬蜱的生命周期包括越冬阶段。我以前的研究表明，一种人类致病菌A。通过选择性诱导肩胛硬蜱中的一种新的抗冻糖蛋白（iafgp），嗜吞噬细胞原虫与其节肢动物载体建立了共生关系，以提高在寒冷中的存活率。本研究的目的是了解A.嗜吞噬细胞菌上调IAFgp基因表达是为了其自身的利益和其载体宿主在低温下的存活。

DESCRIPTION (provided by applicant): Ixodes scapularis ticks overwinter in the Northeast and Upper Midwest parts of United States, and transmit various human pathogens that include human anaplasmosis agent Anaplasma phagocytophilum. My preliminary data show that the presence of A. phagocytophilum in ticks increases the ability of I. scapularis to survive in the cold. I have identified an I. scapularis antifreeze glycoprotein, designated as IAFGP and demonstrate, via RNAi knockdown studies, the importance of IAFGP for the survival of ticks in a freezing environment. Transfection studies also show that IAFGP increases the viability of yeast cells subjected to low temperatures. Remarkably, I have found that A. phagocytophilum induce the expression of iafgp and thereby increase the cold tolerance of I. scapularis. These data define a molecular basis for symbiosis between A. phagocytophilum and I. scapularis. The mechanism by which A. phagocytophilum, induce iafgp expression is not understood. Therefore studies will be performed to elucidate the mechanism by which A. phagocytophilum influence vector gene expression for its own benefit as well as its vector host survival during freezing temperatures. Following are the specific aims that will be addressed to understand the mechanism: In aim 1, I will identify and characterize iafgp promoter in I. scapularis. The studies in this aim will address whether iafgp promoter is activated upon A. phagocytophilum infection. In aim 2, studies will be undertaken to characterize the role of host transcriptional activators that may be involved in iafgp promoter induction. Collectively, the proposed studies not only elucidate the molecular mechanisms of symbiotic association between A. phagocytophilum and I. scapularis ticks but also delineate a new approach to study host-pathogen interaction. PUBLIC HEALTH RELEVANCE: In United States, the life-cycle of Ixodes scapularis ticks that transmit several human pathogens involves overwintering stages. My previous studies show that a human pathogenic bacterium A. phagocytophilum establishes a symbiotic relationship with its arthropod vector to enhance survival in the cold, via the selective induction of a novel antifreeze glycoprotein (iafgp) in Ixodes scapularis. The goal of this proposal is to understand the mechanism by which A. phagocytophilum up-regulate iafgp gene expression for its own benefit and for its vector host survival in the cold temperature.