Role of Vector antioxidant factors in Amblyomma-Rickettsia interaction

描述(申请人提供)：扁虱和其他以血液为食的节肢动物媒介，通过从其多功能唾液腺分泌分子来操纵宿主的自我平衡反应。在它们寻找血食、扁虱和其他食血节肢动物媒介的过程中， 将病原体传播给它们的脊椎动物宿主。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。了解病媒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策略。此外，鉴定那些对取食和传播至关重要的壁虱蛋白对于开发针对壁虱传播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)感染的壁虱蛋白是疫苗和/或药物开发的潜在候选者。我们的长期目标是通过干扰媒介蛋白来减少媒介传播的立克次体疾病的传播。这项R15拨款申请的总体目标是阐明新发现的硒蛋白在硬蜱生理学和斑点热群立克次体(SFGR)传播中的生物学功能。在这项应用中，我们将检验我们的中心假设，即壁虱抗氧化因子(硒蛋白)通过防止血液喂养期间的氧化应激和保护入侵的立克次体而发挥重要的生理作用。这一假设将通过结合生物化学、生理学、遗传学和细胞生物学研究来实现以下具体目标来检验。1)通过防止氧化应激和炎症反应，研究Amblyomma SelenoProteins在硬蜱饲养成功中的生理功能；2)破坏硬蜱体内的氧化平衡，以评估硬蜱饲养成功和一种新的斑点热群立克次体(SFGR)向宿主传播的情况。这项拟议的工作具有创新性，因为病媒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扁虱传播疾病的一种很有前途的策略。这个R15研究项目的结果有望证明扁虱唾液中抗氧化因子的耗尽是否提供了一种新的机制来消除扁虱媒介中的SFGR。 公共卫生相关性：拟议的研究很重要，因为它们代表了一种方法，以了解重要的硬质媒介/立克次体相互作用，这些相互作用有助于立克次体传播潜力，适用于所有立克次体/媒介相互作用。这项拟议的研究与保护公众健康有关，因为了解斑点热群立克次体传播可以加强旨在阻止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.