Extracellular matrix adhesins of Treponema pallidum

性状（由申请人提供）：梅毒螺旋体引起 梅毒螺旋体苍白球，是一种慢性细菌感染 这仍然是全球公共卫生问题，估计有1200万人 发展中国家、东欧和南部非洲报告的新病例 美国的在缺乏适当抗生素治疗的情况下，T.螺旋体 建立一个终身的慢性感染，可能会发展到衰弱 在大约三分之一的感染者中， 个体除了疾病本身的严重性外， 研究表明，梅毒感染可能会增加获得的风险， 人类免疫缺陷病毒的传播。建立一个 T.苍白球感染是细菌附着和上皮细胞定植 表面。因此，提出了预防T.梅毒螺旋体感染 是开发抑制细菌附着于宿主细胞的方法。 本建议中概述的研究重点是T。 参与宿主细胞附着的苍白球粘附素，特别是那些 参与附着于细胞外基质（ECM）的成分。的 T.苍白球将通过多种实验方法进行鉴定， 技术，包括亲和层析和表达文库筛选。 假定的粘附素将使用异源的重组蛋白以重组形式表达。 表达系统。随后将研究这些蛋白质的 参与宿主细胞附着，通过确定它们与 宿主细胞和ECM组分。将对确认的粘附素进行检测， 补充非粘附密螺旋体T的能力。噬菌体生物型Reiter， 密螺旋体粘附素和ECM成分的分子区域 将确定附件的负责人。霸王苍白球粘附素将 还分析了它们在兔免疫中的免疫保护潜力 和挑战性的实验，特别是他们的能力， 密螺旋体感染本报告中概述的研究的长期目标 建议对T.苍白球ECM粘附素，这反过来又有助于 进一步加深了我们对T.螺旋体 发病机制和确定潜在的梅毒疫苗候选者。

DESCRIPTION (Provided by the applicant): Syphilis, caused by the spirochete bacterium Treponema pallidum subsp. pallidum, is a chronic bacterial infection that remains a public health concern worldwide, with an estimated 12 million new cases reported in developing nations, Eastern Europe, and the Southern United States. In the absence of appropriate antibiotic treatment, T. pallidum establishes a lifelong chronic infection that may progress to the debilitating and potentially fatal tertiary disease in approximately one third of infected individuals. Apart from the serious nature of the disease itself, a number of studies suggest syphilis infections may increase the risk of acquisition and transmission of human immunodeficiency virus. The first step in establishing a T. pallidum infection is bacterial attachment and colonization of epithelial surfaces. Consequently, a logical approach for preventing T. pallidum infection is to develop methodologies for inhibiting bacterial attachment to host cells. The studies outlined in this proposal focus upon the identification of T. pallidum adhesins involved in host cell attachment, and specifically those involved in attaching to components of the extracellular matrix (ECM). The adhesins of T. pallidum will be identified using a variety of experimental techniques, including affinity chromatography and expression library screening. Putative adhesins will be expressed in a recombinant form using heterologous expression systems. These proteins will subsequently be investigated for their involvement in host cell attachment by determining their binding potential to host cells and ECM components. Confirmed adhesins will be tested for their ability to complement the non-adherent treponeme T. phagedenis biotype Reiter, and the molecular regions of the treponemal adhesins and ECM components responsible for attachment will be identified. The T. pallidum adhesins will also be analyzed for their immunoprotective potential in rabbit immunization and challenge experiments, and specifically for their ability to prevent treponemal infection. The long-term objective of the studies outlined in this proposal is to identify T. pallidum ECM-adhesins, which will in turn help to further our under-standing of the molecules involved in T. pallidum pathogenesis and identify potential syphilis vaccine candidates.