CRYOELECTRON TOMOGRAPHIC ANALYSIS OF TREPONEMA PALLIDUM

该子项目是利用 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH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 中心，不一定是研究者的机构。 摘要： 梅毒螺旋体（Treponema pallidum）是一种不可培养的螺旋体，可引起性病梅毒，是一种性传播疾病，也是人类的一种专性病原体。梅毒仍然是美国和全球的一个主要公共卫生问题，也被公认为是人类免疫缺陷病毒性传播的一个重要辅助因素。 多年来，我们已经发表了大量的论文，证明T。苍白球具有独特的分子结构。螺旋体的外膜含有少量的跨膜蛋白，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保护T。苍白球从宿主免疫系统中分离出来（因此我们将其命名为“隐形病原体”），但它也提出了远未理解的生理问题，特别是因为细菌的基因组序列不包含良好表征的OM蛋白的直系同源物（例如，孔蛋白）。 解决营养物质穿越T.我们发现了TP 0453，一种具有两亲性螺旋的外膜锚定脂蛋白。考虑到营养物质通过T细胞的途径有限。苍白球外膜，我们假设它是在非常接近细胞质膜，其中包含所需的穿梭分子进入细胞质的转运。我们相信，冷冻电子断层扫描将给我们一个更准确的图片的外和细胞质膜的物理关系，从而促进我们的努力，以了解T的生理方面。在分子水平上的苍白球-宿主相互作用。

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.