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Although antibiotic resistance in environmental bacteria is ancient, resistance in human pathogens is thought to be a modern phenomenon that is driven by the clinical use of antibiotics\n                    <jats:sup>1<\/jats:sup>\n                    . Here we show that particular lineages of methicillin-resistant\n                    <jats:italic>Staphylococcus aureus<\/jats:italic>\n                    \u2014a notorious human pathogen\u2014appeared in European hedgehogs in the pre-antibiotic era. Subsequently, these lineages spread within the local hedgehog populations and between hedgehogs and secondary hosts, including livestock and humans. We also demonstrate that the hedgehog dermatophyte\n                    <jats:italic>Trichophyton erinacei<\/jats:italic>\n                    produces two \u03b2-lactam antibiotics that provide a natural selective environment in which methicillin-resistant\n                    <jats:italic>S. aureus<\/jats:italic>\n                    isolates have an advantage over susceptible isolates. Together, these results suggest that methicillin resistance emerged in the pre-antibiotic era as a co-evolutionary adaptation of\n                    <jats:italic>S. aureus<\/jats:italic>\n                    to the colonization of dermatophyte-infected hedgehogs. The evolution of clinically relevant antibiotic-resistance genes in wild animals and the connectivity of natural, agricultural and human ecosystems demonstrate that the use of a One Health approach is critical for our understanding and management of antibiotic resistance, which is one of the biggest threats to global health, food security and development.\n                  <\/jats:p>","DOI":"10.1038\/s41586-021-04265-w","type":"journal-article","created":{"date-parts":[[2022,1,5]],"date-time":"2022-01-05T13:09:16Z","timestamp":1641388156000},"page":"135-141","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":272,"title":["Emergence of methicillin resistance predates the clinical use of antibiotics"],"prefix":"10.1038","volume":"602","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0582-0457","authenticated-orcid":false,"given":"Jesper","family":"Larsen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claire L.","family":"Raisen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3882-3585","authenticated-orcid":false,"given":"Xiaoliang","family":"Ba","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas J.","family":"Sadgrove","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8300-6891","authenticated-orcid":false,"given":"Guillermo F.","family":"Padilla-Gonz\u00e1lez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monique S. 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