Discovery of the first human endosymbiont

发现第一个人类内共生体

基本信息

批准号：
10706181
负责人：
NEAL DAVID EPSTEIN
金额：
$ 58.21万
依托单位：
NATIONAL HEART, LUNG, AND BLOOD INSTITUTE
依托单位国家：
美国
项目类别：
财政年份：
资助国家：
美国
起止时间：
至
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10706181
关键词：
Alleles Antibodies Arthropods Autoimmune Diseases Back Bacteria Base Sequence Bioinformatics Biology COVID-19 pandemic Cell Nucleus Cell surface Cells China Computer software Cytoplasm Detection Development Disease Evolution Failure Health Human Human Microbiome Immunochemistry In Situ Individual Insecta Investigation Journals Label Laboratories Life Malignant Neoplasms Measures Modification Morphologic artifacts Mothers Nematoda Nerve Degeneration Nucleic Acids Nutritional Operative Surgical Procedures Organism Pattern Physiological Play Preparation Production Protein Engineering Proteins Protocols documentation Publishing Research Personnel Resources Role SARS-CoV-2 spike protein Sampling Skin Time Tissues Vaccines Variant Vertical Disease Transmission Work Yang adult stem cell base cell motility contig egg endosymbiont experimental study fungus genome wide association study human tissue immune function light microscopy novel protein aminoacid sequence symbiont vaccine development volunteer wasting

项目摘要

Endosymbionts are unicellular organisms that reside inside the cells of a host organism and can have dramatic influence over the host, ranging from nutritional provisioning to immune function and in the case of filarial nematodes, their actual development. It is estimated that more than 75% of insects are hosts to endosymbionts which are passed from mother to progeny through the egg. Most of these endosymbionts identified to date are a form of a free living bacteria, although fungi have been described as well. There have been no endosymbionts identified in phyla above Arthropoda. With respect to the presence of primary endosymbionts which are present in the egg, causing vertical transmission to progeny, endosymbionts are distinct from the organisms that make up the human microbiome project. In the latter case, the organisms do not reside inside cells but rather on the surface of cells i.e., on the skin or within the lumen of the gut. We have identified the first human endosymbiont and generated a novel antibody which detects it. The existence of endosymbionts in human tissue is not readily apparent without the antibody, explaining why they have not been seen previously. The antibody identifies their presence in the human egg and allows the detection of the organism within foci of nucleated cells in most tissues. The organism has also been isolated and shown to be facultative free living and will grow extremely slowly under special conditions. Endosymbionts, in general have coevolved with their hosts and through modifications in both host and symbiont manage to inhabit the host and allow it to continue live and reproduce, lest the symbiont die as well. We have labeled the isolated endosymbiont and added it back to primary cultures of human cells, showing that the organism enters the cell and distributes itself in the nucleus and cytoplasm. This pattern replicates what is seen in immunohistochemical studies of human tissue using the same antibody. Based on the biology and physiologic effects of endosymbionts in arthropods, it is likely that this organism plays a role in both human health and disease. This most likely is determined by an interaction between the endosymbiont and the hosts allelic variations in the proteins with which the endosymbiont interacts. Theoretically, there may also be variations and evolution of the endosymbionts as they are passed down individual human maternal lines. In this regard, using the antibody, we have performed preliminary investigations and found differences in the distribution of the endosymbionts in examples of cancer, autoimmune disease and neurodegeneration compared to normal controls. This year additional preparations have been generated and 2700 contigs are being evaluated to generate novel antibodies to this organism.

内共生体是驻留在宿主有机体细胞内的单细胞生物，可以对宿主产生巨大影响，从营养供应到免疫功能，以及在丝状线虫的情况下，其实际发育。据估计，超过75％的昆虫是从母亲到后代通过卵的宿主。迄今为止确定的这些内共生体大多数是一种自由活细菌的一种形式，尽管也已经描述了真菌。在节肢动物上方的门中未发现内共生体。在卵中存在的原发性内共生体的存在中，导致垂直传播到后代，内共生体与构成人类微生物组项目的生物不同。在后一种情况下，生物体不驻留在细胞内，而是位于细胞表面，即皮肤或肠道的腔内。我们已经确定了第一个人内共生体，并生成了一种检测它的新型抗体。没有抗体，人类组织中内共生体的存在并不容易显现，这解释了为什么以前没有看到它们。抗体鉴定出它们在人卵中的存在，并允许在大多数组织中成核细胞的焦点内检测生物体。该生物也已被隔离并证明是自由生活的生活，在特殊条件下会非常缓慢地生长。总体而言，内共生体与宿主共同发展，并通过宿主和Symbiont的修改设法居住在宿主身上，并允许其继续生存和繁殖，以免Symbiont Die也死了。我们已经标记了孤立的内共生体，并将其添加到人类细胞的原代培养物中，表明有机体进入细胞并在细胞核和细胞质中分布自身。这种模式复制了使用相同抗体对人体组织的免疫组织化学研究所见。基于内共生体在节肢动物的生物学和生理影响，这种生物可能在人类健康和疾病中起作用。这很可能取决于内共生体和宿主在与内共生体相互作用的蛋白质中的等位基因变化之间的相互作用。从理论上讲，内共生体被降低了单个人类母体线时，内共生体也可能存在变化和演变。在这方面，使用抗体，我们进行了初步研究，发现与正常对照相比，在癌症，自身免疫性疾病和神经变性的例子中，内共生体的分布有所不同。今年已经产生了其他准备工作，正在评估2700个重叠群，以生成对该生物体的新抗体。