Lyme arthritis virulence of Borrelia burgdorferi

描述（由申请人提供）：莱姆病是一种复杂的多系统疾病，由伯氏疏螺旋体引起，是北美最常见的病媒传播疾病。莱姆关节炎是主要表现之一。在小鼠模型中，包括关节炎在内的几个特征与人类莱姆病相似。在严重联合免疫缺陷（SCID）小鼠模型中，B.伯氏感染会引起破坏性关节炎。B的基因组。burgdorferi由一条染色体和多达21个线性和环状质粒组成。B的离体繁殖。伯氏菌与质粒丢失有关，质粒丢失伴随着感染性和致病性的降低。我们已经产生了一种螺旋体变体，它在SCID小鼠中具有完全感染性，但在该模型中不能诱导关节炎。质粒含量分析显示，四个质粒，目前在关节炎的毒力菌株已失踪的非致病性的变种，这表明这些质粒可能携带关节炎的毒力基因。我们将首先确定哪些质粒是诱导关节炎所必需的。为了实现这一目标，将产生具有不同质粒含量的变体，并检查其感染性和关节炎毒力。一旦关节炎相关的质粒被确定，我们将能够专注于关节炎毒力基因。关节炎病毒质粒上编码的独特基因将被选择性灭活，然后补充，以检查这些基因对关节炎诱导的影响。

DESCRIPTION (provided by applicant): Lyme disease is a complex multisystem disorder caused by the spirochete Borrelia burgdorferi and the most common vector-borne illness in North America. Lyme arthritis is one of the major manifestations. Several features that parallel human Lyme disease are consistently induced in the murine model, including arthritis. In the model of severe combined immunodeficiency (SCID) mice, B. burgdorferi infection causes destructive arthritis. The genome of B. burgdorferi consists of a chromosome and up to 21 linear and circular plasmids. In vitro propagation of B. burgdorferi is associated with plasmid loss and loss of plasmids is coupled with decreased infectivity and pathogenicity. We have generated a spirochete variant that is fully infectious in SCID mice but unable to induce arthritis in this model. Plasmid content analysis revealed that four plasmids that were present in arthritis-virulent strains had been missing from the nonpathogenic variant, suggesting that these plasmids may carry arthritis-virulent genes. We will first determine which of the plasmids are essential for the induction of arthritis. To achieve this goal, variants with different plasmid contents will be generated and examined for infectivity and arthritis virulence. Once arthritis-related plasmids are identified, we will be able to focus on arthritis-virulent genes. Unique genes encoded on the arthritis-virulent plasmids will be selectively inactivated and then complemented to examine the influence of these genes on the induction of arthritis.