CRYOELECTRON TOMOGRAPHIC ANALYSIS OF TREPONEMA PALLIDUM

梅毒螺旋体的冷电子断层扫描分析

• 批准号: 7721722
• 负责人: Justin D Radolf
• 金额: $ 2.22万
• 依托单位: WADSWORTH CENTER
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-02-01 至 2009-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7721722
• 关键词: Antigens; Architecture; Bacteria; Cell membrane; Computer Retrieval of Information on Scientific Projects Database; Cytoplasm; Funding; Genomics; Globus Pallidus; Gram-Negative Bacteria; Grant; HIV; Helix (Snails); Human; Immune system; Institution; Lipoproteins; Membrane; Molecular; Numbers; 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; ear helix; 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: eponema 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.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 抽象的： Eponema Pallidum是导致性传播障碍和人类病原体的性质疾病的不可培养的螺旋体。梅毒仍然是美国和全球的一个主要公共卫生问题，也被广泛认为是人类免疫缺陷病毒性传播的重要联合因素。 多年来，我们发表了许多论文，证明帕利德姆具有独特的分子体系结构。螺旋体的外膜含有跨膜蛋白的稀少，而生物体的主要免疫原（其中许多是脂蛋白）与细胞质膜有关。这种不寻常的分子结构可保护颗粒链球菌免受宿主免疫系统的影响（因此，我们将其称为“隐身病原体”），但它也构成了远离理解的生理问题，尤其是因为细菌的基因组序列不包含良好的OM蛋白（例如，gracteriia bac）的矫形器，而不是构造良好的OM蛋白。 通过发现TP0453（一种带有两亲性螺旋的外膜锚定的脂蛋白），已经提供了跨T. pallidum外膜的养分谜的部分解决方案。鉴于营养物质越过颗粒外膜的含量有限，我们假设它非常接近细胞质膜，该膜包含将分子穿过细胞质所需的转运蛋白。我们认为，冷冻电子层析成像将使我们对外部和细胞质膜的物理关系有更准确的了解，从而进一步努力理解分子水平上pallidum-host相互作用的生理方面。