Identifying Borrelia turicatae genes needed for colonization and transmission fro

描述（由申请方提供）：复发性发热螺旋体病是一种全球性疾病，由软壳蜱或人体虱子传播。在全世界，如果不加以治疗，这种疾病会造成严重的发病率和死亡率，主要影响资源贫乏国家的人们。然而，关于螺旋体从蜱媒介传播到脊椎动物宿主的分子机制知之甚少。因此，为了解决NIAID在改善全球健康方面的作用，我的这项提案的目标是确定遗传因素，使一种回归热螺旋体，疏螺旋体，定殖蜱，并随后传播到哺乳动物宿主。此外，在B之间有几个区别。尿酸盐和莱姆病致病螺旋体，它们制造B。turiclactone有利于研究螺旋体-宿主相互作用。这些差异包括质粒的稳定性和体外培养后感染性的保留，以及在哺乳动物血液中达到高细菌密度的能力。这些区别有助于拟定研究的发展，重点是确定蜱定殖和传播B期间外膜蛋白（Omps）的必要性。turicalus从它的蜱媒介，Ornithodoros turicata。编码Omps的基因家族的重要性已经在不同种类的回归热螺旋体（Borrelia hermsii）中确立。然而，人们对Omps在其他导致疾病的物种中的作用知之甚少。因此，我建议鉴定编码在B内上调的Omp的基因。蜱虫感染期间的尿酸排泄。将使用基于微阵列的方法来鉴定这些遗传决定因素，并确定它们对蜱定殖和传播至哺乳动物的必要性。为了实现这一点，我开发了B中的第一个系统。turiclavirus进行基因失活和互补，并建立了唯一已知的实验室蜱菌落这些研究。这些发现将产生广泛的影响，从而能够开发阻断这种疾病传播的治疗方法，并将增加我们对媒介传播病原体的适应和传播机制的理解。

DESCRIPTION (provided by applicant): Relapsing fever spirochetosis is a global disease transmitted by argasid (soft-shelled) ticks or the human body louse. Throughout the world, this disease causes severe morbidity and mortality if left untreated, primarily affecting those in resource poor countries. However, little is known regarding the molecular mechanisms involved with transmission of the spirochetes from the tick vector to the vertebrate host. Therefore, to address NIAID's role in improving global health, my goal for this proposal is to identify the genetic factors that enable a species of relapsing fever spirochetes, Borrelia turicatae, to colonize the tick and to be subsequently transmitted to the mammalian host. Furthermore, there are several distinctions between B. turicatae and Lyme disease-causing spirochetes which make B. turicatae advantageous for studying spirochete-host interactions. These differences include plasmid stability and retention of infectivity after prolonged in vitro cultivation, and the ability to reach high bacterial densities in mammalian blood. These distinctions have aided in the development of the proposed studies focusing on determining the necessity of outer membrane proteins (Omps) during tick colonization and transmission of B. turicatae from its tick vector, Ornithodoros turicata. The importance of a family of genes which code for Omps has been established in a different species of relapsing fever spirochetes, Borrelia hermsii. However, little is known about the role of Omps in other species that cause disease. Therefore, I propose to identify genes which code for Omps that are up-regulated within B. turicatae during tick infection. A microarray based approach will be used to identify these genetic determinants, and their necessity for tick colonization and transmission to the mammal will be determined. To accomplish this, I have developed the first system in B. turicatae for gene inactivation and complementation, and have established the only known laboratory tick colony for these studies. These findings will have a broad impact enabling the development of therapeutics blocking transmission of this disease, and will increase our understanding of the adaptation and transmission mechanisms of vector-borne pathogens.