ROLE OF T PALLIDUM MSP-HOMOLOGUES IN CNS INVASION

本申请的目标是检验两个假设：a）T. 苍白球分离物含有具有增强的能力的生物群体， 侵袭CNS;和B）神经侵袭的能力由以下物质赋予： 特异性表面蛋白的表达。具体而言，该项目的目标 1）比较T.内苍白球亚群 2）建立高侵袭性T. 苍白球群体; 3）证明表面蛋白的直接参与 在体内介导神经侵袭; 4）确定哪些肿瘤最常见 T.具有神经侵袭性的苍白球生物; 5） 鉴定优先由神经侵袭性生物表达的蛋白质; 6)研究Tpr蛋白和蛋白质的直接参与 在体外和体内使用特异性靶点5在神经侵袭中鉴定 模型本申请中提出的研究可能最终有助于 梅毒疫苗的开发，并可能导致识别能力， 神经侵袭风险最高的病人这些调查是最 适用于同时感染HIV-1的人，因为他们最多 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.