Understanding Unique Aspects of Motility and Chemotaxis in Borrelia burgdorferi

描述（由申请方提供）：螺旋体是一种具有医学意义但知之甚少的细菌。这些微生物引起几种重要的人类疾病，如梅毒、莱姆病和钩端螺旋体病。螺旋体是非常多样化的，但它们有一个特殊的属性：螺旋体可以在一种高粘性的凝胶状介质中游动，例如在结缔组织中发现的介质，这种介质抑制了大多数其他运动细菌的运动。运动性和趋化性是致病性螺旋体的重要毒力因子。然而，由于缺乏遗传工具和螺旋体的挑剔生长，运动和趋化性的基本生物学及其在疾病过程中的作用知之甚少。伯氏疏螺旋体（Borrelia burgdorferi，Bb）是莱姆病的病原体，莱姆病是美国最流行的蜱传疾病。除了作为一个重要的临床实体，Bb是最好的理解螺旋体之一，其中遗传工具在过去几年中迅速发展。该建议的目标是利用Bb作为遗传模型来阐明螺旋体运动性和趋化性的独特方面，以及它们在疾病过程中的作用。为了实现这一目标，本研究的主要目标是：（1）以Bb为遗传模型，阐明螺旋体运动和趋化的分子机制。(2)探讨运动性和趋化性在Bb侵染过程中的作用。从这项研究中获得的结果将导致更好地理解螺旋体运动性和趋化性的基本生物学，以及它们在疾病过程中的作用，这最终可能导致预防和治疗疾病的新手段（例如，开发靶向Bb运动性和趋化性的关键要素的疫苗或抑制剂）。致病性螺旋体，如莱姆病螺旋体伯氏疏螺旋体，是高度运动和侵入性的。本研究的目的是了解螺旋体运动和趋化的基本生物学，以及它们在疾病发病机制中的作用。所获得的结果可能导致疾病预防和治疗的新手段。

DESCRIPTION (provided by applicant): Spirochetes are a medically significant but poorly understood group of bacteria. These organisms cause several important human diseases, such as syphilis, Lyme disease and leptospirosis. Spirochetes are very diverse, but they share a special attribute: Spirochetes can swim in a highly viscous, gel-like medium, such as that found in connective tissue, that inhibits the motility of most other motile bacteria. It is believed that the motility and chemotaxis are very important virulence factors in the pathogenic spirochetes. However, the basic biology of motility and chemotaxis and their roles in the process of the diseases are poorly understood due to the paucity of genetic tools and the fastidious growth of spirochetes. The spirochete Borrelia burgdorferi (Bb) is the causative agent of Lyme disease, which is the most prevalent tick-borne disease in the Unites States. In addition to being an important clinical entity, Bb is one of the best understood spirochetes and one for which genetic tools have rapidly evolved in the past few years. The goal of this proposal is to utilize Bb as a genetic model to elucidate the unique aspects of spirochete motility and chemotaxis, as well as their roles in the process of the disease. To achieve this goal, this proposal focuses on the following specific aims: (1) To elucidate the molecular mechanisms involved in the unique aspects of spirochete motility and chemotaxis by using Bb as a genetic model. (2) To determine the roles of motility and chemotaxis in the infection processes of Bb. The results obtained from this study will lead to better understanding the basic biology of spirochete motility and chemotaxis, as well as their roles in the processes of the disease, which could eventually lead to new means for the prevention and treatment of the disease (e.g., developing vaccines or inhibitors that target the key elements of Bb motility and chemotaxis). The pathogenic spirochetes, such as the Lyme disease spirochete Borrelia burgdorferi, are highly motile and invasive. The goal of this project is to understand the basic biology of spirochete motility and chemotaxis, and their roles in the pathogenesis of the diseases. The obtained results may lead to new means of disease prevention and treatment.