Borrelia burgdorferi interactions with Ixodes scapularis

伯氏疏螺旋体与肩胛硬蜱的相互作用

• 批准号: 8260312
• 负责人: Erol Fikrig
• 金额: $ 39.24万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1994
• 资助国家: 美国
• 起止时间: 1994-05-01 至 2013-10-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8260312
• 关键词: Animals; Antibodies; Antigen Targeting; Antigens; Arthropods; Binding; Biological Assay; Black-legged Tick; Borrelia burgdorferi; Complement; Data; Goals; Health; Human; Imaging Techniques; Immunization; Infection; Infection prevention; Label; Lead; Libraries; Life; Lyme Disease; Lyme Disease Vaccines; Mediating; Medical; Modeling; Modification; Mus; Nature; Order Spirochaetales; OspC protein; Prevention strategy; Proteins; Publications; Saliva; Salivary Glands; Salivary Proteins; Spirochaetales Infections; Techniques; Ticks; Two-Dimensional Gel Electrophoresis; United States; Vaccines; Vector-transmitted infectious disease; Yeasts; high risk; in vivo; killings; microbial; novel strategies; pathogen; prevent; research study; transmission process; vector

DESCRIPTION (provided by applicant): The goal of this proposal is to better understand the intimate relationship between Borrelia burgdorferi, the Lyme disease agent, and one of its major tick vectors, Ixodes scapularis -- in order to develop novel strategies to prevent infection. We postulate that B. burgdorferi use tick salivary proteins (Salps) to facilitate infection of the mammalian host -- and this model is supported by our publication (Nature 436: 573-77, 2005) showing that spirochetes bind I. scapularis Salp15 during transmission from ticks, and that B. burgdorferi then use Salp15 to facilitate infection of mice. We now hypothesize that tick Salps that interact with B. burgdorferi may serve as targets for vaccines to prevent Lyme disease. We will develop this paradigm using, but not limited to, Salp15 as a model tick antigen. First, we will explore how B. burgdorferi use Salp15 to facilitate infection of the mammalian host. Second, we will determine whether B. burgdorferi rely solely on Salp15 to enhance infection of mice, or if the spirochetes also bind to, and use, additional tick Salps during transmission. Indeed, our preliminary data suggests that spirochetes adhere to several proteins in tick saliva. Third, and most importantly, we will determine whether immunization with a tick Salp - again using Salp15 as the first model antigen - can serve as a vaccine to prevent Lyme disease. We hope to show that arthropod proteins - critical for microbial survival in the mammalian host - can serve as targets for a pathogen-specific vaccine. If successful, these data may lead to new strategies for the prevention of B. burgdorferi infection, and this paradigm would also be applicable to other vector-borne pathogens of medical importance. PUBLIC HEALTH RELEVANCE: Lyme disease is the most common tick-borne illness in the United States. The causative agent is Borrelia burgdorferi, a spirochete. The goal of this proposal is to develop a better appreciation of the intimate relationship between Borrelia burgdorferi and its tick vector, Ixodes scapularis. The Lyme disease agent binds to several tick proteins during its transmission from ticks to mice or humans. By understanding these spirochete-tick interactions in greater detail, we will develop new ways to interfere with transmission of the Lyme disease agent. We hope to show that tick proteins - essential for B. burgdorferi survival in the mammalian host - can serve as targets for a Lyme disease vaccine. If successful, these studies may lead to new strategies for the prevention of B. burgdorferi infection. This paradigm would also be applicable to other vector-borne pathogens of medical importance.

描述（由申请人提供）：该提案的目的是更好地了解Borrelia Burgdorferi，Lyme Disease Ament及其主要tick媒介之一ixodes capapularis之间的亲密关系，以制定新的策略来防止感染。我们假设B. burgdorferi使用tick唾液蛋白（salps）来促进哺乳动物宿主的感染 - 该模型得到了我们的出版物（自然436：573-77，2005）的支持，表明螺旋体显示I. scapularis salp15在从tick虫传输过程中，并使用B. burgdorferi salpertiti salpitate salpitate salpitate salpitate salpitate salpitate salpitate。现在，我们假设与B. burgdorferi相互作用的tick味可以作为预防莱姆病的疫苗的靶标。我们将使用但不限于SALP15作为模型tick抗原来开发此范式。首先，我们将探讨B. Burgdorferi如何使用SALP15来促进哺乳动物宿主的感染。其次，我们将确定B. burgdorferi是否仅依靠SALP15来增强小鼠的感染，或者螺旋体在传播过程中也与螺旋体结合并使用额外的tick味。确实，我们的初步数据表明，螺旋体粘附在tick唾液中的几种蛋白质。第三，也是最重要的是，我们将确定用tick salp的免疫 - 再次使用SALP15作为第一个模型抗原 - 可以用作预防莱姆病的疫苗。我们希望表明，节肢动物蛋白（对于哺乳动物宿主中的微生物生存至关重要）可以作为病原体特异性疫苗的靶标。如果成功，这些数据可能会导致预防B. burgdorferi感染的新策略，并且该范式也将适用于其他医学重要性的媒介传播病原体。 公共卫生相关性：莱姆病是美国最常见的tick传播疾病。因果剂是螺旋体Borrelia Burgdorferi。该提案的目的是更好地欣赏Borrelia Burgdorferi与其tick矢量Ixodes capapularis之间的亲密关系。莱姆病剂在从小鼠或人类传播的过程中与多种tick蛋白结合。通过更详细地了解这些螺旋体棘手的相互作用，我们将开发新的方法来干扰莱姆病的传播。我们希望证明tick蛋白 - 哺乳动物宿主中的B. burgdorferi生存至关重要 - 可以作为莱姆病疫苗的靶标。如果成功的话，这些研究可能会导致预防B. burgdorferi感染的新策略。该范式也适用于其他具有医学重要性的媒介传播病原体。

项目成果

Tick microbiome: the force within.

• DOI: 10.1016/j.pt.2015.03.010
• 发表时间: 2015-07
• 期刊: Trends in parasitology
• 影响因子: 9.6
• 作者: Narasimhan S;Fikrig E
• 通讯作者: Fikrig E

Tick histamine release factor is critical for Ixodes scapularis engorgement and transmission of the lyme disease agent.

• DOI: 10.1371/journal.ppat.1001205
• 发表时间: 2010-11-24
• 期刊: PLoS pathogens
• 影响因子: 6.7
• 作者: Dai J;Narasimhan S;Zhang L;Liu L;Wang P;Fikrig E
• 通讯作者: Fikrig E

Molecular interactions that enable movement of the Lyme disease agent from the tick gut into the hemolymph.

分子相互作用使莱姆病病原体从蜱肠道移动到血淋巴中。

• DOI: 10.1371/journal.ppat.1002079
• 发表时间: 2011
• 期刊: PLoS pathogens
• 影响因子: 6.7
• 作者: Zhang,Lili;Zhang,Yue;Adusumilli,Sarojini;Liu,Lei;Narasimhan,Sukanya;Dai,Jianfeng;Zhao,YangO;Fikrig,Erol
• 通讯作者: Fikrig,Erol

Factor Xa activation of factor V is of paramount importance in initiating the coagulation system: lessons from a tick salivary protein.

• DOI: 10.1161/circulationaha.113.003191
• 发表时间: 2013-07-16
• 期刊: Circulation
• 影响因子: 37.8
• 作者: Schuijt TJ;Bakhtiari K;Daffre S;Deponte K;Wielders SJ;Marquart JA;Hovius JW;van der Poll T;Fikrig E;Bunce MW;Camire RM;Nicolaes GA;Meijers JC;van 't Veer C
• 通讯作者: van 't Veer C

Preferential protection of Borrelia burgdorferi sensu stricto by a Salp15 homologue in Ixodes ricinus saliva.

• DOI: 10.1086/591917
• 发表时间: 2008-10-15
• 期刊: The Journal of infectious diseases
• 作者: Hovius JW;Schuijt TJ;de Groot KA;Roelofs JJ;Oei GA;Marquart JA;de Beer R;van 't Veer C;van der Poll T;Ramamoorthi N;Fikrig E;van Dam AP
• 通讯作者: van Dam AP