Lyme arthritis virulence of Borrelia burgdorferi

伯氏疏螺旋体的莱姆关节炎毒力

• 批准号: 7193375
• 负责人: FANG-TING LIANG
• 金额: $ 7.14万
• 依托单位: LOUISIANA STATE UNIV A&M COL BATON ROUGE
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-03-01 至 2009-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7193375
• 关键词: Acrodermatitis; Affect; Animal Model; Arthritis; Benign Migratory Glossitis; Black-legged Tick; Borrelia; Borrelia burgdorferi; Carditis; Chromosomes; Complement; Complex; Coupled; Cutaneous; Disease; Evolution; Genes; Genome; Goals; Human; Immune; Immune Sera; Immune response; Immunocompetent; In Vitro; Infection; Lesion; Lyme Arthritis; Lyme Disease; Mammals; Mediating; Modeling; Mus; Neurologic; North America; Order Spirochaetales; Passive Immunization; Pathogenicity; Plasmids; Resolution; Severe Combined Immunodeficiency; Surface Antigens; Ticks; Tissues; Variant; Virulence; Virulent; Week; day; mouse model; vector

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.

描述（由申请人提供）：莱姆病是一种由伯氏疏螺旋体螺旋体引起的复杂的多系统疾病，也是北美最常见的媒介传播疾病。莱姆关节炎是其主要表现之一。在小鼠模型中始终诱导出与人类莱姆病相似的几个特征，包括关节炎。在严重联合免疫缺陷 (SCID) 小鼠模型中，伯氏疏螺旋体感染会导致破坏性关节炎。伯氏疏螺旋体的基因组由一条染色体和多达 21 个线性和环状质粒组成。伯氏疏螺旋体的体外繁殖与质粒丢失有关，而质粒丢失又会导致感染性和致病性下降。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，但无法在此模型中诱导关节炎。质粒内容分析显示，关节炎毒力菌株中存在的四个质粒在非致病性变体中缺失，表明这些质粒可能携带关节炎毒力基因。我们将首先确定哪些质粒对于诱导关节炎是必需的。为了实现这一目标，将产生具有不同质粒内容的变体并检查其感染性和关节炎毒力。一旦鉴定出与关节炎相关的质粒，我们将能够专注于关节炎毒力基因。关节炎毒力质粒上编码的独特基因将被选择性失活，然后进行补充，以检查这些基因对关节炎诱导的影响。