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Principal Investigator: NEAL DAVID EPSTEIN
Organization: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE
Fiscal Year: 2022
Award: $582,088
Funding agency: National Heart Lung and Blood Institute
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.
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