Coinfection by Rickettsiae in Amblyomma maculatum: Impact on Disease Transmission

描述(申请人提供)：落基山斑疹热在近一个世纪前在美国成为可报告的，目前病例处于最高水平。然而，在美国，人们并没有广泛认识到立克次体以外的立克次体可以引起斑点性FEVR。尽管在过去20年中已经发现了其他斑点热群立克次体(SFGR)，但在现有的“斑点热立克次体病”流行病学知识方面仍然存在空白，CDC现在使用“斑点热立克次体病”来代替落基山斑点热。帕氏立克次体是由斑纹夜蛾传播的，它最近成为斑点热立克次体病的致病因素。然而，在斑点念珠菌中也发现了一种新的SFGR，即“Candidatus Rickettsia andeanae”，人们对此知之甚少，其疾病含义也尚不清楚。在斑点立克次体-SFGR系统中，相同种类的立克次体之间的相互作用如何影响立克次体的传播和维持还没有被探索过。事实上，这种硬质立克次体系统可能不同于先前描述的有关革螨和SFGR的系统。本研究的长期目标是以斑点伊蚊-SFGR系统为模型，了解斑点热立克次体的生物学特性及其相互关系，以便更准确地刻画斑点热立克次体病的复杂流行病学。为了实现这一目标，本R15区域应用程序的总体目标是通过了解斑点立克次体中这些SFGR在以脊椎动物为食的蜱类动物中的相互作用来评估斑点立克次体中的帕氏杆菌和“Andeanae”对斑点热立克次体的潜在贡献。中心假说是，“安氏卡氏杆菌”不会传染，但会影响帕氏杆菌的传播和维持。这项拟议研究的基本原理是，了解除立克次体外的SFGR如何导致疾病，以及对立克次体的传播和维持，将有助于澄清斑点热立克次体病的流行病学。斑点立克次体-SFGR系统提供了一个理想的模型，用来评估壁虱和立克次体之间的相互作用。为了与区域目标保持一致，学生将参与建议的 在不接触高致病性物种的情况下研究新兴的病媒生物。在这一修订的R15应用中，提出了两个目标以实现目标：(1)评估单独和共同感染的斑点拟线虫和帕克氏杆菌的组织嗜性，以及“安迪纳氏杆菌”对帕克氏弧菌传播的影响(S)；(2)评估共同摄食和“安迪亚卡氏杆菌”在使扁虱能够获得帕克雷伯氏菌方面的存在。这项拟议的研究具有重要意义，因为它促进了对潜在的新型立克次体相互作用的进一步了解。这些知识将有助于准确评估斑点热立克次体病流行病学数据。最终，对这些数据的合理解释将有助于公共卫生政策的制定。最后，这项拟议的研究是创新的，因为初步数据挑战了所有壁虱传播的SFGR中都存在经卵巢干扰的假设，这表明联合感染可能在某些系统中占优势。因此，节肢动物中的微生物相互作用可能比目前认为的更复杂。

DESCRIPTION (provided by applicant): Rocky Mountain spotted fever became reportable in the United States nearly a century ago and cases are currently at their highest levels. However, it is not widely recognized that rickettsiae other than Rickettsia rickettsii can cause spotted fevr in the United States. Although other spotted fever group rickettsiae (SFGR) have been identified over the last two decades, there remains a gap in existing knowledge of the epidemiology of "spotted fever rickettsiosis," nomenclature CDC now uses in place of Rocky Mountain spotted fever. Rickettsia parkeri, which is transmitted by Amblyomma maculatum, recently emerged as a contributor to spotted fever rickettsiosis. However, "Candidatus Rickettsia andeanae," a novel SFGR also present in A. maculatum, is poorly understood and its disease implications unknown. How interactions between sympatric rickettsiae within the same tick species may affect rickettsial transmission and maintenance, has not been explored in the A. maculatum-SFGR system. In fact, this tick-rickettsial system may differ from those previously described for Dermacentor ticks and SFGR. The long-term goal of this research is to understand the biology and relationships between SFGR in ticks, using the A. maculatum-SFGR system as a model, in order to more accurately portray the complex epidemiology of spotted fever rickettsiosis. To move toward this goal, the overall objective of this R15 AREA application is to evaluate the potential contribution of R. parkeri and "Ca. R. andeanae" in A. maculatum to spotted fever rickettsiosis by understanding interactions between these SFGR in A. maculatum during tick feeding on vertebrates. The central hypothesis is that "Ca. R. andeanae" will not be infectious but will affect transmission and maintenance of R. parkeri. The rationale for the proposed research is that understanding how SFGR other than R. rickettsii contribute to disease, and to transmission and maintenance of rickettsiae, will help clarify spotted fever rickettsiosis epidemiology. The A. maculatum-SFGR system provides an ideal model with which to evaluate tick-rickettsia interactions. In keeping with AREA goals, students will participate in the proposed research on emerging vector-borne organisms without being exposed to highly pathogenic species. In this revised R15 application, two Aims are proposed to accomplish the goals: (1) to evaluate tissue tropism of "Ca. R. andeanae" and R. parkeri in singly and co-infected A. maculatum, and effect(s) of "Ca. R. andeanae" on transmission of R. parkeri; and (2) to evaluate co-feeding and "Ca. R. andeanae" presence in enabling tick acquisition of R. parkeri. The proposed research is significant because it promotes further understanding of potentially novel tick-rickettsia interactions. This knowledge will assist in accurately evaluating spotted fever rickettsiosis epidemiologic data. Ultimately, rational interpretation of these data will be useful in public health policy making. Finally, the proposed research is innovative because preliminary data challenge the presumption that transovarial interference occurs in all tick-borne SFGR, suggesting that co-infections may prevail in some systems. Thus, microbial interactions in arthropods may be more complex than is currently believed.