Influence of Inflammation on B burgdorferi Adaptation

描述（由申请人提供）：伯氏疏螺旋体，莱姆病螺旋体，维持在涉及蜱虫媒介和哺乳动物的复杂的动物生命周期中。螺旋体适应这些不同的环境，部分是通过选择性基因表达。温度、pH值和营养等环境因素影响伯氏疏螺旋体基因在体外的表达。通过对受感染小鼠皮肤中脂蛋白基因表达的分析，确定了两种明显不同的伯氏疏螺旋体适应微环境：初始状态和免疫状态。在初始状态下，伯氏疏螺旋体表达116个脂蛋白基因，而在慢性感染时仅表达34个。伯氏疏螺旋体能够侵入哺乳动物宿主的几乎所有器官和组织，这些不同的微环境可能影响其脂蛋白基因的表达。这种病原体引起小鼠心脏炎和关节炎，与人类莱姆病的两种主要表现相似。目前尚不清楚炎症是否会影响伯氏疏螺旋体的适应。本项目将采用小鼠模型研究伯氏疏螺旋体脂蛋白基因的组织差异表达及炎症对其脂蛋白基因表达的影响。为实现这些目标，将完成以下具体目标。

DESCRIPTION (provided by the applicant): Borrelia burgdorferi, the Lyme disease spirochete, is maintained within a complex enzootic life cycle involving the tick vector and the mammal. The spirochete adapts to these diverse environments, in part, by selective gene expression. Environmental cues such as temperature, pH and nutrients influence in vitro B. burgdorferi gene expression. Analysis of the gene expression of lipoproteins in the infected murine skin has defined two remarkably different microenvironments for B. burgdorferi adaptation: naive status and immune status. In the naive state, B. burgdorferi expresses 116 of its lipoprotein genes while only 34 of them are expressed during chronic infection. B. burgdorferi is able to invade almost all organs and tissues of the mammalian host and these diverse microenvironments may influence its lipoprotein gene expression. This pathogen causes murine carditis and arthritis that parallel two major manifestations of human Lyme disease. It is unknown whether inflammation influences B. burgdorferi adaptation. In this project, the tissue differential expression of lipoprotein genes and the influence of inflammation on lipoprotein gene expression of B. burgdorferi will be investigated using the murine model. To achieve these goals, the following specific aims will be completed. 1. To investigate the tissue differential expression of B. burgdorferi lipoprotein genes in the bladder, heart and joint during murine infection; 2. To examine the influence of inflammation on B. burgdorferi adaptation.