ROLE OF T PALLIDUM MSP-HOMOLOGUES IN CNS INVASION

这个应用程序的目标是检验两个假设：a)T。 梅毒分离株包含具有增强能力的有机体种群 侵袭中枢神经；以及b)神经侵袭的能力是由 特定表面蛋白的表达。具体地说，这个项目的目标 1)比较梅毒螺旋体各亚群的神经侵袭能力。 2)建立高神经侵袭性T。 梅毒的种群；3)证明了表面蛋白的直接参与 在体内调节神经侵袭；4)确定哪些TPR最常见 由具有神经侵袭性的梅毒螺旋体转录和表达；5) 确定神经侵袭性生物优先表达的蛋白质； 6)研究Tpr蛋白和蛋白的直接参与 利用体外和体内实验鉴定神经侵袭的特异性靶点5 模特们。本申请中提出的研究可能最终有助于 梅毒疫苗的开发，可能导致识别梅毒的能力 神经侵袭风险最高的患者。这些调查是大多数 适用于同时感染艾滋病毒-1的人，因为他们最多 有患梅毒和神经梅毒的风险。

The goal of this application is to test two hypotheses: a) T. pallidum isolates contain populations of organisms with enhanced ability to invade the CNS; and b) The capacity for neuroinvasion is conferred by expression of specific surface proteins. Specifically, the Aims of this project are: 1) Compare the neuroinvasive capacity of T. pallidum subpopulations within strains using in vivo and in vitro models; 2) Establish highly neuroinvasive T. pallidum populations; 3) Demonstrate the direct involvement of surface proteins in mediating neuroinvasion in vivo; 4) Determine which tprs are most frequently transcribed and expressed by T. pallidum organisms that are neuroinvasive; 5) Identify proteins that are preferentially expressed by neuroinvasive organisms; 6) Investigate the direct involvement of the Tpr proteins and the proteins identified in Specific Aim 5 in neuroinvasion using in vitro and in vivo models. The studies proposed in this application may ultimately contribute to development of a vaccine for syphilis and may lead to the ability to identify patients at the highest risk for neuroinvasion. These investigations are most applicable to persons who are also infected with HIV-1, as they are at greatest risk for syphilis and neurosyphilis.