Role of Vector antioxidant factors in Amblyomma-Rickettsia interaction

描述（由申请人提供）：蜱和其他吸血节肢动物载体通过从其多功能唾液腺分泌分子来操纵宿主体内平衡反应。在寻找吸血食物、蜱虫和其他吸血节肢动物的过程中， 将病原体传播给脊椎动物宿主。立克次体病是媒介传播疾病的一个很好的例子，其在公共卫生中的重要性被低估了。了解媒介和病原体之间的相互作用可能有助于制定防治节肢动物传播感染的战略。此外，表征那些对摄食和传播至关重要的蜱蛋白对于开发针对蜱传病原体的新疫苗和疗法的分子基础至关重要。影响斑点热群立克次体（SFGR）成功感染的蜱蛋白代表了疫苗和/或药物开发的潜在候选者。我们的长期目标是通过干扰载体蛋白来减少媒介传播的立克次体病的传播。这项R15资助申请的总体目标是阐明新鉴定的硒蛋白在蜱生理学和斑点热群立克次体（SFGR）传播中的生物学功能。在这个应用程序中，我们将测试我们的中心假设，蜱抗氧化因子（硒蛋白）发挥重要的生理作用，防止氧化应激在血液喂养和保护入侵立克次体剂。这一假设将通过使用生物化学、生理学、遗传学和细胞生物学研究的组合追求以下具体目标来检验。1)探讨钝眼蜱硒蛋白通过抑制氧化应激和炎症反应在蜱类摄食成功中的生理功能。2）通过破坏蜱体内的氧化平衡来评估蜱类摄食成功和一种新的斑点热群立克次体（SFGR）向宿主的传播。拟议的工作是创新的，因为媒介传播的病原体容易受到氧化应激的影响;干扰氧化还原代谢是预防蜱传疾病的一种有前途的策略。这项R15研究项目的结果有望证明蜱唾液中抗氧化因子的耗尽是否提供了一种消除蜱媒介中SFGR的新机制。 公共卫生相关性：拟议的研究是重要的，因为它们代表了一种方法，以了解显着的蜱媒/立克次体的相互作用，有助于立克次体的传播潜力，适用于所有立克次体/媒介的相互作用。拟议的研究与保护公共卫生有关，因为了解斑点热群立克次体传播可以加强旨在阻断立克次体传播的研究。

DESCRIPTION (provided by applicant): Ticks, and other blood-feeding arthropod vectors, manipulate host homeostatic responses by secreting molecules from their multifunctional salivary glands. In their quest for a blood meal, ticks, and other blood-feeding arthropod vectors, transmit pathogens to their vertebrate hosts. Rickettsiosis is a great example of vector-borne diseases whose importance in public health is underappreciated. Understanding the interactions between vector and pathogen might help in developing strategies to combat arthropod-borne infections. Moreover, characterizing those tick proteins critical for feeding and transmission is essential to developing a molecular basis for new vaccines and therapeutics against tick-borne pathogens. Tick proteins that influence successful Spotted Fever Group Rickettsia (SFGR) infection represent potential candidates for vaccine and/or drug development. Our long-term goal is to reduce the spreading of vector- borne rickettsial disease by interfering with vector proteins. The overall objective of this R15 grant application is to elucidate the biological functin of newly identified selenoproteins in tick physiology and Spotted Fever Group Rickettsia (SFGR) transmission. In this application, we will test our central hypothesis that tick antioxidant factor (Selenoproteins) play an important physiological role by preventing oxidative stress during blood-feeding and protects invading rickettsial agents. This hypothesis will be tested by pursuing the following specific aims using a combination of biochemical, physiological, genetic and cell biological studies. 1) Investigate the physiological function of Amblyomma Selenoproteins in tick feeding success by preventing oxidative stress and inflammation, 2) Disrupt the oxidative balance in the tick to evaluate the tick feeding success and a novel Spotted Fever Group Rickettsia (SFGR) transmission to the host. The proposed work is innovative because the vector-borne pathogens are susceptible to oxidative stress; interference with redox metabolism represents a promising strategy for preventing tick-borne diseases. Results from this R15 research project are expected to demonstrate whether depletion of antioxidant factors in the tick saliva provide a new mechanism to eliminate the SFGR in tick vectors. PUBLIC HEALTH RELEVANCE: The proposed studies are important because they represent an approach to understanding significant tick vector/rickettsial interactions that contribute to rickettsial transmission potential with applicability to all Rickettsia/vector interactions. The proposed research is relevant to protecting public health because understanding spotted fever group rickettsia transmission could enhance research aimed at blocking Rickettsial transmission.