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Here, we study <jats:italic>E. faecalis<\/jats:italic> isolates ranging from the pre-antibiotic era in 1936 up to 2018, covering a large set of host species including wild birds, mammals, healthy humans, and hospitalised patients. We sequence the bacterial genomes using short- and long-read techniques, and identify multiple extant hospital-associated lineages, with last common ancestors dating back as far as the 19th century. We find a population cohesively connected through homologous recombination, a metabolic flexibility despite a small genome size, and a stable large core genome. Our findings indicate that the apparent hospital adaptations found in hospital-associated <jats:italic>E. faecalis<\/jats:italic> lineages likely predate the \u201cmodern hospital\u201d era, suggesting selection in another niche, and underlining the generalist nature of this nosocomial pathogen.<\/jats:p>","DOI":"10.1038\/s41467-021-21749-5","type":"journal-article","created":{"date-parts":[[2021,3,9]],"date-time":"2021-03-09T11:03:14Z","timestamp":1615287794000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":109,"title":["Apparent nosocomial adaptation of Enterococcus faecalis predates the modern hospital era"],"prefix":"10.1038","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3160-2042","authenticated-orcid":false,"given":"Anna K.","family":"P\u00f6ntinen","sequence":"first","affiliation":[]},{"given":"Janetta","family":"Top","sequence":"additional","affiliation":[]},{"given":"Sergio","family":"Arredondo-Alonso","sequence":"additional","affiliation":[]},{"given":"Gerry","family":"Tonkin-Hill","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7326-4133","authenticated-orcid":false,"given":"Ana R.","family":"Freitas","sequence":"additional","affiliation":[]},{"given":"Carla","family":"Novais","sequence":"additional","affiliation":[]},{"given":"Rebecca A.","family":"Gladstone","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3399-2136","authenticated-orcid":false,"given":"Maiju","family":"Pesonen","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1632-1752","authenticated-orcid":false,"given":"Rodrigo","family":"Meneses","sequence":"additional","affiliation":[]},{"given":"Henri","family":"Pesonen","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5360-1254","authenticated-orcid":false,"given":"John A.","family":"Lees","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5703-9315","authenticated-orcid":false,"given":"Dorota","family":"Jamrozy","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8094-3751","authenticated-orcid":false,"given":"Stephen D.","family":"Bentley","sequence":"additional","affiliation":[]},{"given":"Val F.","family":"Lanza","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3709-1690","authenticated-orcid":false,"given":"Carmen","family":"Torres","sequence":"additional","affiliation":[]},{"given":"Luisa","family":"Peixe","sequence":"additional","affiliation":[]},{"given":"Teresa M.","family":"Coque","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7069-5958","authenticated-orcid":false,"given":"Julian","family":"Parkhill","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1894-7545","authenticated-orcid":false,"given":"Anita C.","family":"Sch\u00fcrch","sequence":"additional","affiliation":[]},{"given":"Rob J. 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