Extracellular matrix adhesins of Treponema pallidum

梅毒螺旋体细胞外基质粘附素

• 批准号: 6876048
• 负责人: CAROLINE E CAMERON
• 金额: $ 26.01万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-04-15 至 2007-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6876048
• 关键词: Treponema; Treponema pallidum; adhesin; affinity chromatography; antigen antibody reaction; bacteria infection mechanism; enzyme linked immunosorbent assay; expression cloning; extracellular matrix; gene expression; genetic library; host organism interaction; immunization; laboratory rabbit; male; protein binding; protein protein interaction; syphilis

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.

描述（由申请人提供）： 梅毒，由螺旋体引起 细菌梅毒螺旋体亚种。梅毒，是一种慢性细菌感染 这仍然是全世界的一个公共卫生问题，估计有 1200 万人 发展中国家、东欧和南部地区报告了新病例 美国。如果没有适当的抗生素治疗，梅毒螺旋体 造成终生慢性感染，可能会导致衰弱 大约三分之一的感染者可能患有致命的三级疾病 个人。除了疾病本身的严重性外，许多 研究表明梅毒感染可能会增加感染和梅毒的风险 人类免疫缺陷病毒的传播。建立机构的第一步 梅毒螺旋体感染是细菌附着和定植于上皮细胞 表面。因此，预防梅毒螺旋体感染的合理方法 是开发抑制细菌附着于宿主细胞的方法。 本提案中概述的研究重点是 T 的鉴定。 参与宿主细胞附着的苍白球粘附素，特别是那些 参与细胞外基质 (ECM) 成分的附着。这 梅毒螺旋体的粘附素将通过多种实验来鉴定 技术，包括亲和层析和表达库筛选。 假定的粘附素将使用异源以重组形式表达 表达系统。随后将研究这些蛋白质的作用 通过确定它们的结合潜力来参与宿主细胞附着 宿主细胞和 ECM 成分。确认的粘附剂将进行测试 补充非粘附性密螺旋体噬菌体生物型 Reiter 的能力， 以及密螺旋体粘附素和 ECM 成分的分子区域 将确定附件的负责人。梅毒螺旋体粘附素将 还可以分析其在兔子免疫中的免疫保护潜力 和挑战实验，特别是他们阻止的能力 密螺旋体感染。本研究概述的长期目标 提议是鉴定梅毒螺旋体 ECM 粘附素，这反过来将有助于 进一步我们对梅毒螺旋体相关分子的理解 发病机制并确定潜在的梅毒候选疫苗。