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The host manipulation tools that evolved in the interaction with protozoa confer these bacteria the capacity to also infect phylogenetically distinct eukaryotic cells, such as macrophages, and thus they can also be human pathogens. To manipulate the host cell, bacteria use protein secretion systems and molecular effectors. Although these molecular effectors are encoded in bacteria, they are expressed and function in a eukaryotic context often mimicking or inhibiting eukaryotic proteins. Indeed, many of these effectors have eukaryotic-like domains. In this review, we propose that the main pathways that environmental intracellular bacteria need to subvert in order to establish the host eukaryotic cell as a replication niche are chromatin remodelling, ubiquitination signalling and modulation of protein\u2013protein interactions via tandem repeat domains. We then provide mechanistic insight into how these proteins might have evolved. Finally, we highlight that in environmental intracellular bacteria the number of eukaryotic-like domains and proteins is considerably higher than in intracellular bacteria specialized to an isolated niche, such as obligate intracellular human pathogens. As mimics of eukaryotic proteins are critical components of host\u2013pathogen interactions, this distribution of eukaryotic-like domains suggests that the environment has selected them.<\/jats:p>","DOI":"10.1093\/femsre\/fuac012","type":"journal-article","created":{"date-parts":[[2022,2,14]],"date-time":"2022-02-14T15:21:59Z","timestamp":1644852119000},"source":"Crossref","is-referenced-by-count":45,"title":["The evolution and role of eukaryotic-like domains in environmental intracellular bacteria: the battle with a eukaryotic cell"],"prefix":"10.1093","volume":"46","author":[{"given":"Jessica E","family":"Martyn","sequence":"first","affiliation":[{"name":"Institut Pasteur, Universit\u00e9 de Paris, CNRS UMR 6047 Unit\u00e9 Biologie des Bact\u00e9ries Intracellulaires , Paris , France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Gomez-Valero","sequence":"additional","affiliation":[{"name":"Institut Pasteur, Universit\u00e9 de Paris, CNRS UMR 6047 Unit\u00e9 Biologie des Bact\u00e9ries Intracellulaires , Paris , France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3477-9190","authenticated-orcid":false,"given":"Carmen","family":"Buchrieser","sequence":"additional","affiliation":[{"name":"Institut Pasteur, Universit\u00e9 de Paris, CNRS UMR 6047 Unit\u00e9 Biologie des Bact\u00e9ries Intracellulaires , Paris , France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2022,2,16]]},"reference":[{"key":"2022070202264574100_bib1","doi-asserted-by":"crossref","first-page":"1526","DOI":"10.1093\/molbev\/msu111","article-title":"High fitness costs and instability of gene duplications reduce rates of evolution of new genes by duplication-divergence mechanisms","volume":"31","author":"Adler","year":"2014","journal-title":"Mol Biol 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