CRYOELECTRON TOMOGRAPHIC ANALYSIS OF TREPONEMA PALLIDUM

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 摘要： 梅毒螺旋体是一种不可培养的螺旋体，可引起性病，这是一种性传播疾病，也是人类的一种专性病原体。梅毒在美国和全球仍然是一个主要的公共卫生问题，也被公认为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。螺旋体的外膜含有很少的跨膜蛋白，而生物体的主要免疫原，其中许多是脂蛋白，与细胞质膜有关。这种不同寻常的分子结构保护梅毒螺旋体免受宿主免疫系统的攻击(因此我们将其命名为“隐形病原体”)，但它也提出了远未被了解的生理问题，特别是因为细菌的基因组序列不包含来自革兰氏阴性细菌的特征良好的OM蛋白(例如，孔蛋白)的同源基因。我们发现了TP0453，这是一种外膜锚定的脂蛋白，具有两亲性螺旋，为解决梅毒螺旋体外膜营养物质运输之谜提供了部分解决方案。鉴于营养物质穿过梅毒螺旋体外膜的途径有限，我们假设它离细胞膜非常近，细胞膜包含将分子运送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为我们提供更准确的外膜和细胞质膜物理关系的图像，从而进一步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。

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.