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Metabolic intermediates, such as those in the TCA cycle, have been known to be linked to bacterial virulence. L\u2010Malic acid (L\u2010MA), a natural TCA cycle intermediate, is known for its antimicrobial and antioxidant properties; however, its effect on the virulence of\n                    <jats:styled-content style=\"fixed-case\">\n                      <jats:italic>Staphylococcus aureus<\/jats:italic>\n                    <\/jats:styled-content>\n                    has yet to be explored. It was found that L\u2010malic acid not only inhibited bacterial growth but also markedly reduced the production of crucial virulence factors, including staphyloxanthin and \u03b1\u2010hemolysin. The suppression of pigment synthesis was primarily due to the competitive antagonism of CrtO, a key oxidoreductase responsible for carotenoid biosynthesis in\n                    <jats:styled-content style=\"fixed-case\">\n                      <jats:italic>Staphylococcus aureus<\/jats:italic>\n                    <\/jats:styled-content>\n                    , coupled with enhanced flux through the TCA cycle that redirected acetyl\u2010CoA pools away from the mevalonate pathway. Moreover, hemolytic activity was decreased by lowering the expression of \u03b1\u2010hemolysin. In\u00a0vivo studies using mouse infection models further demonstrated that L\u2010malic acid effectively mitigated the pathogenicity of\n                    <jats:styled-content style=\"fixed-case\">\n                      <jats:italic>Staphylococcus aureus<\/jats:italic>\n                    <\/jats:styled-content>\n                    , significantly reducing the formation of skin and liver abscesses. These findings position L\u2010malic acid as a promising agent targeting\n                    <jats:styled-content style=\"fixed-case\">\n                      <jats:italic>Staphylococcus aureus<\/jats:italic>\n                    <\/jats:styled-content>\n                    infections, highlighting the need for further research into its therapeutic potential.\n                  <\/jats:p>","DOI":"10.1096\/fj.202600917r","type":"journal-article","created":{"date-parts":[[2026,5,30]],"date-time":"2026-05-30T10:55:16Z","timestamp":1780138516000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Targeting of Staphyloxanthin and \u03b1\u2010Hemolysin by Natural Compound L\u2010Malic Acid Suppresses\n                    <i>Staphylococcus aureus<\/i>\n                    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