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The mobile<jats:italic>cfr<\/jats:italic>gene was identified in European veterinary isolates from the late 1990s, although the earliest report of a clinical<jats:italic>cfr<\/jats:italic>-positive strain was the 2005 Colombian methicillin-resistant<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Staphylococcus aureus<\/jats:named-content>(MRSA) isolate CM05. Here, through retrospective analysis of LZD<jats:sup>r<\/jats:sup>clinical strains from a U.S. surveillance program, we identified a<jats:italic>cfr<\/jats:italic>-positive MRSA isolate, 1128105, from January 2005, predating CM05 by 5 months. Molecular typing of 1128105 revealed a unique pulsed-field gel electrophoresis (PFGE) profile most similar to that of USA100,<jats:italic>spa<\/jats:italic>type t002, and multilocus sequence type 5 (ST5). In addition to<jats:italic>cfr<\/jats:italic>, LZD resistance in 1128105 is partially attributed to the presence of a single copy of the 23S rRNA gene mutation T2500A. Transformation of the \u223c37-kb conjugative p1128105<jats:italic>cfr<\/jats:italic>-bearing plasmid from 1128105 into<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">S. aureus<\/jats:named-content>ATCC 29213 background strains was successful in recapitulating the Cfr antibiogram, as well as resistance to aminoglycosides and trimethoprim. A 7-kb<jats:italic>cfr<\/jats:italic>-containing region of p1128105 possessed sequence nearly identical to that found in the Chinese veterinary<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Proteus vulgaris<\/jats:named-content>isolate PV-01 and in U.S. clinical<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">S. aureus<\/jats:named-content>isolate 1900, although the presence of IS<jats:italic>431<\/jats:italic>-like sequences is unique to p1128105. The<jats:italic>cfr<\/jats:italic>gene environment in this early clinical<jats:italic>cfr<\/jats:italic>-positive isolate has now been identified in Gram-positive and Gram-negative strains of clinical and veterinary origin and has been associated with multiple mobile elements, highlighting the versatility of this multidrug resistance gene and its potential for further dissemination.<\/jats:p>","DOI":"10.1128\/aac.03493-14","type":"journal-article","created":{"date-parts":[[2014,8,26]],"date-time":"2014-08-26T06:40:17Z","timestamp":1409035217000},"page":"6592-6598","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":32,"title":["Linezolid-Resistant Staphylococcus aureus Strain 1128105, the First Known Clinical Isolate Possessing the<i>cfr<\/i>Multidrug Resistance Gene"],"prefix":"10.1128","volume":"58","author":[{"given":"Jeffrey B.","family":"Locke","sequence":"first","affiliation":[{"name":"Trius Therapeutics, Inc., San Diego, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Douglas E.","family":"Zuill","sequence":"additional","affiliation":[{"name":"Trius Therapeutics, Inc., San Diego, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caitlyn R.","family":"Scharn","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology and Immunology, Creighton University School of Medicine, Omaha, Nebraska, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"Deane","sequence":"additional","affiliation":[{"name":"Eurofins Global Central Laboratory, Chantilly, Virginia, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel F.","family":"Sahm","sequence":"additional","affiliation":[{"name":"Eurofins Global Central Laboratory, Chantilly, Virginia, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerald A.","family":"Denys","sequence":"additional","affiliation":[{"name":"Indiana University Health Pathology Laboratory, Indianapolis, Indiana, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard V.","family":"Goering","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology and Immunology, Creighton University School of Medicine, Omaha, Nebraska, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen J.","family":"Shaw","sequence":"additional","affiliation":[{"name":"Trius Therapeutics, Inc., San Diego, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.05702-11"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(00)04376-2"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(01)05410-1"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01032-09"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.49.8.3554-3557.2005"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2958.2007.05744.x"},{"key":"e_1_3_2_8_2","volume-title":"Abstr. 20th Eur. 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