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We previously discovered\n                      <jats:italic toggle=\"yes\">farR<\/jats:italic>\n                      through\n                      <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                      selection for increased resistance to linoleic acid, leading to recovery of FarR\n                      <jats:sup>H121Y<\/jats:sup>\n                      that promoted enhanced expression of\n                      <jats:italic toggle=\"yes\">farE<\/jats:italic>\n                      . Here, we report on the widespread emergence of increased resistance to linoleic acid across the phylogenetic spectrum of\n                      <jats:italic toggle=\"yes\">S. aureus<\/jats:italic>\n                      through mechanisms that are both dependent and independent of\n                      <jats:italic toggle=\"yes\">farER<\/jats:italic>\n                      . In this latter group, sequence type ST228 healthcare-associated methicillin-resistant\n                      <jats:italic toggle=\"yes\">S. aureus<\/jats:italic>\n                      has FarR\n                      <jats:sup>A14P<\/jats:sup>\n                      that is defective in DNA binding and cannot induce\n                      <jats:italic toggle=\"yes\">farE<\/jats:italic>\n                      expression, and yet these strains exhibit enhanced resistance to linoleic acid. In the former group, we note the polyphyletic emergence of FarR\n                      <jats:sup>G166D<\/jats:sup>\n                      in ST5 community-acquired MRSA (CA-MRSA), adding to previously noted variants FarR\n                      <jats:sup>C116Y<\/jats:sup>\n                      and FarR\n                      <jats:sup>E160G<\/jats:sup>\n                      in ST5 MRSA. We also observe FarR\n                      <jats:sup>H121Y<\/jats:sup>\n                      and FarR\n                      <jats:sup>G166D<\/jats:sup>\n                      in ST97 methicillin-susceptible\n                      <jats:italic toggle=\"yes\">S. aureus<\/jats:italic>\n                      from bovine hosts, together with polyphyletic emergence of FarR\n                      <jats:sup>C116Y<\/jats:sup>\n                      . Last, we note the emergence of FarR\n                      <jats:sup>H121Y<\/jats:sup>\n                      in the USA300 lineage of ST8 CA-MRSA from the UK, in association with an SCC\n                      <jats:italic toggle=\"yes\">mec<\/jats:italic>\n                      VI element that encodes resistance to fusidic acid, a topical antimicrobial used to treat superficial skin infections. Our data support the widespread emergence and dissemination of\n                      <jats:italic toggle=\"yes\">S. aureus<\/jats:italic>\n                      strains from both human and bovine hosts, with enhanced resistance to unsaturated free fatty acids that comprise an important chemical component of innate immunity.\n                    <\/jats:p>\n                    <jats:sec>\n                      <jats:title>IMPORTANCE<\/jats:title>\n                      <jats:p>\n                        <jats:italic toggle=\"yes\">Staphylococcus aureus<\/jats:italic>\n                        is a priority pathogen for the World Health Organization due to its association with human morbidity, mortality, and acquisition of multiple drug resistance. In addition to acquiring specific antimicrobial resistance genes, it is also widely documented that\n                        <jats:italic toggle=\"yes\">S. aureus<\/jats:italic>\n                        can evolve through accumulation of genetic polymorphisms that confer reduced susceptibility to some antibiotics such as daptomycin and vancomycin. In this study, we report on the widespread emergence of\n                        <jats:italic toggle=\"yes\">S. aureus<\/jats:italic>\n                        strains with sufficiency for increased resistance to antimicrobial fatty acids through polymorphisms in the regulator of an efflux pump. This is an indication that, in addition to evolution in response to antibiotics that are used to treat infections,\n                        <jats:italic toggle=\"yes\">S. aureus<\/jats:italic>\n                        also exhibits the capacity to evolve in response to antimicrobial unsaturated fatty acids that are important chemical components of innate immunity. These findings underscore the exceptional capacity of\n                        <jats:italic toggle=\"yes\">S. aureus<\/jats:italic>\n                        to evolve in response to antimicrobial threats.\n                      <\/jats:p>\n                    <\/jats:sec>\n                  <\/jats:sec>","DOI":"10.1128\/spectrum.02278-25","type":"journal-article","created":{"date-parts":[[2025,10,31]],"date-time":"2025-10-31T13:00:14Z","timestamp":1761915614000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":0,"title":["Widespread emergence of\n                    <i>Staphylococcus aureus<\/i>\n                    with variant FarR regulators and enhanced resistance to antimicrobial fatty acids within clonal complex CC5, CC8, and CC97 strains from human and bovine hosts"],"prefix":"10.1128","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-9892-444X","authenticated-orcid":false,"given":"Camryn 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