CRYOELECTRON TOMOGRAPHIC ANALYSIS OF TREPONEMA PALLIDUM

梅毒螺旋体的冷电子断层扫描分析

• 批准号: 7954590
• 负责人: Justin D Radolf
• 金额: $ 2.23万
• 依托单位: WADSWORTH CENTER
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-02-01 至 2010-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7954590
• 关键词: Antigens; Architecture; Bacteria; Biological; Cell membrane; Computer Retrieval of Information on Scientific Projects Database; Cytoplasm; Funding; Genomics; Gram-Negative Bacteria; Grant; HIV; Human; Imagery; Immune system; Institution; Lipoproteins; Membrane; Molecular; Nutrient; Order Spirochaetales; Organism; Orthologous Gene; Paper; Physiological; Proteins; Public Health; Publishing; Research; Research Personnel; Resources; Sexual Transmission; Sexually Transmitted Diseases; Solutions; Source; Syphilis; Treponema pallidum; United States; United States National Institutes of Health; abstracting; electron tomography; pathogen; porin

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. ABSTRACT: Treponema pallidum is the noncultivatable spirochete that causes venereal syphilis, a sexually transmitted disorder and an obligate pathogen of humans. Syphilis remains a major public health problem in the United States and globally and is also well recognized as an important co-factor in the sexual transmission of the human immunodeficiency virus. Over the years, we have published a number of papers demonstrating that T. pallidum has a unique molecular architecture. The spirochete's outer membrane contains a paucity of membrane-spanning proteins while the organism's major immunogens, many of which are lipoproteins, are associated with the cytoplasmic membrane. This unusual molecular architecture protects T. pallidum from the host immune system (hence our designation of it as "the stealth pathogen"), but it also poses physiological issues that are far from understood, especially since the bacterium's genomic sequence does not contain orthologs for well-characterized OM proteins (e.g., porins) from gram-negative bacteria. Part of the solution to the riddle of nutrient transport across the T. pallidum outer membrane has been provided by our discovery of TP0453, an outer membrane-anchored lipoprotein with amphipathic helices. Given the limited means for nutrients to cross the T. pallidum outer membrane, we hypothesize that it is in very close proximity to the cytoplasmic membrane which contains the transporters needed to shuttle molecules into the cytoplasm. We believe that cryo-electron tomography will give us a much more accurate picture of the physical relationship of the outer and cytoplasmic membranes, thereby furthering our efforts to understand the physiologic aspects of T. pallidum-host interactions at the molecular level.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目和 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 抽象的： 梅毒螺旋体是一种不可培养的螺旋体，可引起性病梅毒，这是一种性传播疾病，也是人类的专性病原体。梅毒仍然是美国和全球的一个主要公共卫生问题，也被公认为人类免疫缺陷病毒性传播的重要辅助因素。 多年来，我们发表了多篇论文，证明梅毒螺旋体具有独特的分子结构。螺旋体的外膜含有少量跨膜蛋白，而生物体的主要免疫原（其中许多是脂蛋白）与细胞质膜相关。这种不寻常的分子结构可以保护梅毒螺旋体免受宿主免疫系统的侵害（因此我们将其称为“隐形病原体”），但它也带来了远未了解的生理问题，特别是因为该细菌的基因组序列不包含来自革兰氏阴性细菌的已充分表征的 OM 蛋白（例如孔蛋白）。 我们发现的TP0453（一种具有两亲性螺旋的外膜锚定脂蛋白）为解决穿过梅毒螺旋体外膜的营养物运输之谜提供了部分答案。鉴于营养物质穿过梅毒螺旋体外膜的方式有限，我们假设它非常接近细胞质膜，细胞质膜包含将分子穿梭到细胞质中所需的转运蛋白。我们相信，冷冻电子断层扫描将使我们能够更准确地了解外膜和细胞质膜的物理关系，从而进一步促进我们在分子水平上了解梅毒螺旋体与宿主相互作用的生理方面的努力。