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© The Author(s), 2019. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Hinzke, T., Kleiner, M., Breusing, C., Felbeck, H., Häsler, R., Sievert, S. M., Schlüter, R., Rosenstiel, P., Reusch, T. B. H., Schweder, T., & Markert, S. Host-microbe interactions in the chemosynthetic Riftia pachyptila symbiosis. Mbio, 10(6), (2019): e02243-19, doi:10.1128/mBio.02243-19. ; The deep-sea tubeworm Riftia pachyptila lacks a digestive system but completely relies on bacterial endosymbionts for nutrition. Although the symbiont has been studied in detail on the molecular level, such analyses were unavailable for the animal host, because sequence information was lacking. To identify host-symbiont interaction mechanisms, we therefore sequenced the Riftia transcriptome, which served as a basis for comparative metaproteomic analyses of symbiont-containing versus symbiont-free tissues, both under energy-rich and energy-limited conditions. Our results suggest that metabolic interactions include nutrient allocation from symbiont to host by symbiont digestion and substrate transfer to the symbiont by abundant host proteins. We furthermore propose that Riftia maintains its symbiont by protecting the bacteria from oxidative damage while also exerting symbiont population control. Eukaryote-like symbiont proteins might facilitate intracellular symbiont persistence. Energy limitation apparently leads to reduced symbiont biomass and increased symbiont digestion. Our study provides unprecedented insights into host-microbe interactions that shape this highly efficient symbiosis. ; This work was supported by the German Research Foundation DFG (grant MA 6346/2-1 to S.M., grant BR 5488/1-1 to C.B.), the German Academic Exchange Service DAAD (T.H.), a fellowship of the Institute of Marine Biotechnology Greifswald (T.H.), the Canada Foundation for Innovation, the Government of Alberta and the Natural Sciences and Engineering Research Council of Canada NSERC through a ...