{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,21]],"date-time":"2026-03-21T20:12:31Z","timestamp":1774123951666,"version":"3.50.1"},"reference-count":30,"publisher":"American Society for Microbiology","issue":"1","license":[{"start":{"date-parts":[[2012,2,21]],"date-time":"2012-02-21T00:00:00Z","timestamp":1329782400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-sa\/3.0\/"},{"start":{"date-parts":[[2012,3,1]],"date-time":"2012-03-01T00:00:00Z","timestamp":1330560000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["mBio"],"published-print":{"date-parts":[[2012,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Since its discovery in the early 2000s, methicillin-resistant\n            <jats:named-content content-type=\"genus-species\">Staphylococcus aureus<\/jats:named-content>\n            (MRSA) clonal complex 398 (CC398) has become a rapidly emerging cause of human infections, most often associated with livestock exposure. We applied whole-genome sequence typing to characterize a diverse collection of CC398 isolates (\n            <jats:italic>n<\/jats:italic>\n            = 89), including MRSA and methicillin-susceptible\n            <jats:named-content content-type=\"genus-species\">S. aureus<\/jats:named-content>\n            (MSSA) from animals and humans spanning 19 countries and four continents. We identified 4,238 single nucleotide polymorphisms (SNPs) among the 89 core genomes. Minimal homoplasy (consistency index = 0.9591) was detected among parsimony-informative SNPs, allowing for the generation of a highly accurate phylogenetic reconstruction of the CC398 clonal lineage. Phylogenetic analyses revealed that MSSA from humans formed the most ancestral clades. The most derived lineages were composed predominantly of livestock-associated MRSA possessing three different staphylococcal cassette chromosome\n            <jats:italic>mec<\/jats:italic>\n            element (SCC\n            <jats:italic>mec<\/jats:italic>\n            ) types (IV, V, and VII-like) including nine subtypes. The human-associated isolates from the basal clades carried phages encoding human innate immune modulators that were largely missing among the livestock-associated isolates. Our results strongly suggest that livestock-associated MRSA CC398 originated in humans as MSSA. The lineage appears to have undergone a rapid radiation in conjunction with the jump from humans to livestock, where it subsequently acquired tetracycline and methicillin resistance. Further analyses are required to estimate the number of independent genetic events leading to the methicillin-resistant sublineages, but the diversity of SCC\n            <jats:italic>mec<\/jats:italic>\n            subtypes is suggestive of strong and diverse antimicrobial selection associated with food animal production.\n          <\/jats:p>\n          <jats:p>\n            <jats:bold>IMPORTANCE<\/jats:bold>\n            Modern food animal production is characterized by densely concentrated animals and routine antibiotic use, which may facilitate the emergence of novel antibiotic-resistant zoonotic pathogens. Our findings strongly support the idea that livestock-associated MRSA CC398 originated as MSSA in humans. The jump of CC398 from humans to livestock was accompanied by the loss of phage-carried human virulence genes, which likely attenuated its zoonotic potential, but it was also accompanied by the acquisition of tetracycline and methicillin resistance. Our findings exemplify a bidirectional zoonotic exchange and underscore the potential public health risks of widespread antibiotic use in food animal production.\n          <\/jats:p>","DOI":"10.1128\/mbio.00305-11","type":"journal-article","created":{"date-parts":[[2012,2,22]],"date-time":"2012-02-22T06:27:07Z","timestamp":1329892027000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":615,"title":["Staphylococcus aureus CC398: Host Adaptation and Emergence of Methicillin Resistance in Livestock"],"prefix":"10.1128","volume":"3","author":[{"given":"Lance B.","family":"Price","sequence":"first","affiliation":[{"name":"Translational Genomics Research Institute (TGen), Pathogen Genomics Division, Flagstaff, Arizona, USA"}]},{"given":"Marc","family":"Stegger","sequence":"additional","affiliation":[{"name":"Department of Microbiological Surveillance and Research, Statens Serum Institut, Copenhagen, Denmark"}]},{"given":"Henrik","family":"Hasman","sequence":"additional","affiliation":[{"name":"National Food Institute, Technical University of Denmark, Lyngby, Denmark"}]},{"given":"Maliha","family":"Aziz","sequence":"additional","affiliation":[{"name":"Translational Genomics Research Institute (TGen), Pathogen Genomics Division, Flagstaff, Arizona, USA"}]},{"given":"Jesper","family":"Larsen","sequence":"additional","affiliation":[{"name":"Department of Microbiological Surveillance and Research, Statens Serum Institut, Copenhagen, Denmark"}]},{"given":"Paal Skytt","family":"Andersen","sequence":"additional","affiliation":[{"name":"Department of Microbiological Surveillance and Research, Statens Serum Institut, Copenhagen, Denmark"}]},{"given":"Talima","family":"Pearson","sequence":"additional","affiliation":[{"name":"Center for Microbial Genetics and Genomics, Northern Arizona University, Flagstaff, Arizona, USA"}]},{"given":"Andrew E.","family":"Waters","sequence":"additional","affiliation":[{"name":"Translational Genomics Research Institute (TGen), Pathogen Genomics Division, Flagstaff, Arizona, USA"}]},{"given":"Jeffrey T.","family":"Foster","sequence":"additional","affiliation":[{"name":"Center for Microbial Genetics and Genomics, Northern Arizona University, Flagstaff, Arizona, USA"}]},{"given":"James","family":"Schupp","sequence":"additional","affiliation":[{"name":"Translational Genomics Research Institute (TGen), Pathogen Genomics Division, Flagstaff, Arizona, USA"}]},{"given":"John","family":"Gillece","sequence":"additional","affiliation":[{"name":"Translational Genomics Research Institute (TGen), Pathogen Genomics Division, Flagstaff, Arizona, USA"}]},{"given":"Elizabeth","family":"Driebe","sequence":"additional","affiliation":[{"name":"Translational Genomics Research Institute (TGen), Pathogen Genomics Division, Flagstaff, Arizona, USA"}]},{"given":"Cindy M.","family":"Liu","sequence":"additional","affiliation":[{"name":"Translational Genomics Research Institute (TGen), Pathogen Genomics Division, Flagstaff, Arizona, USA"},{"name":"Center for Microbial Genetics and Genomics, Northern Arizona University, Flagstaff, Arizona, USA"}]},{"given":"Burkhard","family":"Springer","sequence":"additional","affiliation":[{"name":"\u00d6sterreichische Agentur f\u00fcr Gesundheit und Ern\u00e4hrungssicherheit GmbH, Bereich Humanmedizin, Institut f\u00fcr Medizinische Mikrobiologie und Hygiene, Graz, Austria"}]},{"given":"Irena","family":"Zdovc","sequence":"additional","affiliation":[{"name":"Veterinary Faculty, Institute of Microbiology and Parasitology, University of Ljubljana, Ljubljana, Slovenia"}]},{"given":"Antonio","family":"Battisti","sequence":"additional","affiliation":[{"name":"Istituto Zooprofilattico Sperimentale delle Regioni Lazio e Toscana, Rome, Italy"}]},{"given":"Alessia","family":"Franco","sequence":"additional","affiliation":[{"name":"Istituto Zooprofilattico Sperimentale delle Regioni Lazio e Toscana, Rome, Italy"}]},{"given":"Jacek","family":"Z\u0307mudzki","sequence":"additional","affiliation":[{"name":"Department of Swine Diseases, National Veterinary Research Institute, Pulawy, Poland"}]},{"given":"Stefan","family":"Schwarz","sequence":"additional","affiliation":[{"name":"Institute of Farm Animal Genetics, Friedrich-Loeffler-Institut, Neustadt-Mariensee, Germany"}]},{"given":"Patrick","family":"Butaye","sequence":"additional","affiliation":[{"name":"Department of Pathology, Bacteriology, and Poultry Diseases, Faculty of Veterinary Medicine, University of Ghent, Merelbeke, Belgium"},{"name":"Unit of General Bacteriology, Veterinary and Agrochemical Research Centre, Brussels, Belgium"}]},{"given":"Eric","family":"Jouy","sequence":"additional","affiliation":[{"name":"Anses, Ploufragan Plouzan\u00e9 Laboratory, Ploufragan, France"}]},{"given":"Constanca","family":"Pomba","sequence":"additional","affiliation":[{"name":"Interdisciplinary Centre of Research in Animal Health, Faculty of Veterinary Medicine, Lisbon, Portugal"}]},{"given":"M. Concepci\u00f3n","family":"Porrero","sequence":"additional","affiliation":[{"name":"Centro de Vigilancia Sanitaria Veterinaria, Universidad Complutense de Madrid, Madrid, Spain"}]},{"given":"Raymond","family":"Ruimy","sequence":"additional","affiliation":[{"name":"University Paris-Diderot and National Reference Center, Bacterial Resistance in the Commensal Flora, H\u00f4pital Bichat-Claude Bernard, Paris, France"}]},{"given":"Tara C.","family":"Smith","sequence":"additional","affiliation":[{"name":"Center for Emerging Infectious Diseases, University of Iowa, Coralville, Iowa, USA"}]},{"given":"D. Ashley","family":"Robinson","sequence":"additional","affiliation":[{"name":"Department of Microbiology, University of Mississippi Medical Center, Jackson, Mississippi, USA"}]},{"given":"J. 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