{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T05:59:07Z","timestamp":1789106347633,"version":"build-2803163510"},"reference-count":51,"publisher":"Oxford University Press (OUP)","issue":"11","license":[{"start":{"date-parts":[[2025,8,28]],"date-time":"2025-08-28T00:00:00Z","timestamp":1756339200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key R&D program of China","doi-asserted-by":"publisher","award":["2024YFE0199000"],"award-info":[{"award-number":["2024YFE0199000"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32472458"],"award-info":[{"award-number":["32472458"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Natural Science Foundation of Shanghai","award":["24ZR1436200"],"award-info":[{"award-number":["24ZR1436200"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,11,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Staphylococcus aureus, particularly MRSA strains, poses a critical global health threat due to its multidrug resistance and virulence.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>This study elucidates the role of the acnA gene, encoding aconitase in the tricarboxylic acid (TCA) cycle, in governing virulence and antimicrobial resistance in MRSA.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>The identification of the acnA mutant was performed by a transposon mutant library. The function of the acnA gene on virulence was evaluated through deletion and complementation analyses. Other phenotypes of \u0394acnA were also determined, including growth curve, cell wall structure observations using scanning and transmission electron microscopy (SEM\/TEM), cell wall thickness, autolysis and the determination of energy metabolism-associated phenotypes. MICs for BAA1717 and \u0394acnA were determined by antimicrobial susceptibility testing. Finally, virulence- and resistance-related gene expression levels were determined by RT\u2013qPCR.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Deletion of acnA in MRSA strain BAA1717 abolished staphyloxanthin biosynthesis and haemolytic activity, disrupted cell wall integrity and reduced resistance to \u03b2-lactams, aminoglycosides, macrolides and vancomycin, with MICs decreasing by 2- to 128-fold. Structural defects in the cell wall, visualized via SEM and TEM, correlated with heightened autolysis rates. Metabolic dysfunction in the acnA mutant was evident through diminished ATP production, NADPH synthesis and membrane potential. Transcriptional profiling revealed significant downregulation of virulence-related genes (crtO, crtP, hla, hlgA and hlyIII) and resistance determinants (sepA, norA, ftsW, pbps, murC and lytR).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>These findings establish acnA as a metabolic nexus coordinating virulence and antimicrobial resistance in MRSA, highlighting its potential as a therapeutic target to disarm persistent infections through metabolic interference.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/jac\/dkaf317","type":"journal-article","created":{"date-parts":[[2025,8,13]],"date-time":"2025-08-13T11:49:46Z","timestamp":1755085786000},"page":"2934-2944","source":"Crossref","is-referenced-by-count":4,"title":["The pivotal role of\n                    <i>acnA<\/i>\n                    in linking carbon metabolism to virulence and antimicrobial resistance 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