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，在复杂的地方性生活史中维持，涉及壁虱媒介和哺乳动物。螺旋体适应这些不同的环境，部分是通过选择性的基因表达。环境因子如温度、pH和营养物质在体外影响伯氏杆菌基因的表达。对感染小鼠皮肤中脂蛋白基因表达的分析确定了伯氏杆菌适应的两个明显不同的微环境：幼稚状态和免疫状态。在幼稚状态下，伯氏杆菌表达116个脂蛋白基因，而在慢性感染期间只表达34个。伯氏杆菌能够入侵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会影响其脂蛋白基因的表达。这种病原体会引起小鼠心脏炎和关节炎，这与人类莱姆病的两个主要表现相似。目前尚不清楚炎症是否会影响伯氏杆菌的适应。本项目将利用小鼠模型研究伯氏杆菌脂蛋白基因的组织差异表达以及炎症对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。 1.研究伯氏杆菌脂蛋白基因在小鼠感染过程中在膀胱、心脏和关节中的组织差异表达； 2.探讨炎症对伯氏杆菌适应的影响。

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.