{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T13:12:12Z","timestamp":1789650732098,"version":"4.0.0"},"reference-count":53,"publisher":"American Society for Microbiology","license":[{"start":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T00:00:00Z","timestamp":1789603200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T00:00:00Z","timestamp":1789603200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["K22 AI153677, R35 GM154857"],"award-info":[{"award-number":["K22 AI153677, R35 GM154857"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000052","name":"NIH Office of the Director","doi-asserted-by":"publisher","award":["T35 OD011151"],"award-info":[{"award-number":["T35 OD011151"]}],"id":[{"id":"10.13039\/100000052","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["J Bacteriol"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      Metabolic flexibility allows\n                      <jats:italic toggle=\"yes\">Staphylococcus aureus<\/jats:italic>\n                      to survive killing by antibiotics and antimicrobial immune molecules while infecting every niche of the mammalian host. Whether\n                      <jats:italic toggle=\"yes\">S. aureus<\/jats:italic>\n                      is using glycolysis, aerobic respiration, or anaerobic respiration to generate energy, these cellular processes must be accurately attuned to the infected host tissue. Shifting from respiration to glycolysis lowers metabolic throughput, allowing the transition to a persistent\n                      <jats:italic toggle=\"yes\">S. aureus<\/jats:italic>\n                      infection and avoiding killing by most antimicrobial molecules, which typically target rapidly dividing cells. Previously, we reported that arachidonic acid (AA), an abundant host polyunsaturated fatty acid (PUFA), kills\n                      <jats:italic toggle=\"yes\">S. aureus<\/jats:italic>\n                      through a lipid peroxidation mechanism. Here, we report that the extent of PUFA killing of\n                      <jats:italic toggle=\"yes\">S. aureus<\/jats:italic>\n                      can be predicted by the autoxidation rate constant, extending our previous AA findings to include all PUFAs. Contrasting many other antimicrobial molecules, AA kills glycolytic\n                      <jats:italic toggle=\"yes\">S. aureus<\/jats:italic>\n                      more effectively than respiring\n                      <jats:italic toggle=\"yes\">S. aureus<\/jats:italic>\n                      . Elevating cellular ATP levels protects\n                      <jats:italic toggle=\"yes\">S. aureus<\/jats:italic>\n                      from PUFA killing, indicating that glycolytic\n                      <jats:italic toggle=\"yes\">S. aureus<\/jats:italic>\n                      strains cannot sufficiently energize the ATP-dependent processes that allow\n                      <jats:italic toggle=\"yes\">S. aureus<\/jats:italic>\n                      to survive PUFA toxicity. This report defines cellular metabolism as a key determinant in\n                      <jats:italic toggle=\"yes\">S. aureus<\/jats:italic>\n                      PUFA resistance and demonstrates that PUFAs are effective antimicrobials against glycolytic\n                      <jats:italic toggle=\"yes\">S. aureus<\/jats:italic>\n                      , including persister cells and small colony variants. Furthermore, identifying and validating the ATP-dependent processes that protect\n                      <jats:italic toggle=\"yes\">S. aureus<\/jats:italic>\n                      from PUFA killing will define pathways that can be targeted to accentuate killing by the host immune system, leading to the clearance of persistent\n                      <jats:italic toggle=\"yes\">S. aureus<\/jats:italic>\n                      infections.\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                        causes significant human morbidity and mortality. The metabolic diversity of this pathogen makes eradication challenging, leading to persistent infections in many patient populations. Polyunsaturated fatty acids (PUFAs) are host-derived antimicrobial molecules that are abundant at the host-pathogen interface. Here, we define the mechanism of killing by PUFAs in metabolically limited\n                        <jats:italic toggle=\"yes\">S. aureus<\/jats:italic>\n                        strains. These strains are difficult to eradicate because most therapies target rapidly dividing cells. We demonstrate that PUFAs kill slow-growing\n                        <jats:italic toggle=\"yes\">S. aureus<\/jats:italic>\n                        through a lipid peroxidation mechanism better than their normal growth counterparts. Restoring ATP levels in these strains protects against PUFA killing, demonstrating that the PUFA survival response is not fully energized in the low metabolic state.\n                      <\/jats:p>\n                    <\/jats:sec>\n                  <\/jats:sec>","DOI":"10.1128\/jb.00249-26","type":"journal-article","created":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T13:00:40Z","timestamp":1789650040000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":0,"title":["Polyunsaturated fatty acids: host-derived antimicrobials against glycolytic\n                    <i>Staphylococcus aureus<\/i>"],"prefix":"10.1128","author":[{"given":"Alex R.","family":"Stackhouse","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/05ect4e57","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Pathobiological Sciences, Louisiana State University and Agricultural and Mechanical College, School of Veterinary Medicine","place":["Baton Rouge, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Asif","family":"Iqbal","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/05ect4e57","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Pathobiological Sciences, Louisiana State University and Agricultural and Mechanical College, School of Veterinary Medicine","place":["Baton Rouge, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D. Grace","family":"Ross","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/05ect4e57","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Pathobiological Sciences, Louisiana State University and Agricultural and Mechanical College, School of Veterinary Medicine","place":["Baton Rouge, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wyatt W.","family":"Wittliff","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/05ect4e57","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Pathobiological Sciences, Louisiana State University and Agricultural and Mechanical College, School of Veterinary Medicine","place":["Baton Rouge, USA"]},{"id":[{"id":"https:\/\/ror.org\/05ect4e57","id-type":"ROR","asserted-by":"publisher"}],"name":"Louisiana State University School of Veterinary Medicine Mass Spectrometry Resource Center, Louisiana State University and Agricultural and Mechanical College, School of Veterinary 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