{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T15:51:36Z","timestamp":1786117896009,"version":"build-2736575974"},"reference-count":31,"publisher":"American Society for Microbiology","issue":"8","license":[{"start":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T00:00:00Z","timestamp":1785801600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T00:00:00Z","timestamp":1785801600000},"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":["Microbiol Spectr"],"published-print":{"date-parts":[[2026,8,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      Serious\n                      <jats:italic toggle=\"yes\">Staphylococcus aureus<\/jats:italic>\n                      infections pose a major global public health challenge. However, the escalating problem of antibiotic resistance has led to a progressive decline in effective therapeutic options. In this study, we demonstrated that\n                      <jats:italic toggle=\"yes\">Aspergillus aureoles<\/jats:italic>\n                      GGNSJ001, a bioactive compound isolated from endophytic fungi of Kudzu root, effectively inhibits\n                      <jats:italic toggle=\"yes\">S. aureus<\/jats:italic>\n                      biofilm formation\n                      <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                      . Further analysis revealed that the ability of\n                      <jats:italic toggle=\"yes\">S. aureus<\/jats:italic>\n                      to adhere to and invade RAW 264.7 cells was attenuated by\n                      <jats:italic toggle=\"yes\">A. aureoles<\/jats:italic>\n                      GGNSJ001 pre-treatment. To explore the underlying mechanism, an\n                      <jats:italic toggle=\"yes\">S. aureus<\/jats:italic>\n                      -infected macrophage model was established, and the effect of\n                      <jats:italic toggle=\"yes\">A. aureoles<\/jats:italic>\n                      GGNSJ001 on oxidative stress and ferroptosis was assessed. It was shown in the results that the levels of reactive oxygen species (ROS) and malondialdehyde (MDA) were elevated by\n                      <jats:italic toggle=\"yes\">A. aureoles<\/jats:italic>\n                      GGNSJ001 treatment, while the expression of superoxide dismutase (SOD) and glutathione (GSH) was reduced. Through immunofluorescence (IF) and qRT-PCR analyses, it was further confirmed that lipid peroxidation and Fe\n                      <jats:sup>2+<\/jats:sup>\n                      accumulation were promoted, and the expression of key ferroptosis-related genes\n                      <jats:italic toggle=\"yes\">ACSL4<\/jats:italic>\n                      ,\n                      <jats:italic toggle=\"yes\">ALOX15<\/jats:italic>\n                      ,\n                      <jats:italic toggle=\"yes\">TFR1<\/jats:italic>\n                      , and\n                      <jats:italic toggle=\"yes\">GPX4<\/jats:italic>\n                      were reversed by\n                      <jats:italic toggle=\"yes\">A. aureoles<\/jats:italic>\n                      GGNSJ001, leading to effective control of\n                      <jats:italic toggle=\"yes\">S. aureus<\/jats:italic>\n                      infection. Mechanistically, it was identified that ferroptosis driven by the\n                      <jats:italic toggle=\"yes\">NCOA4\u2013FTH1<\/jats:italic>\n                      axis constitutes the core event through which the antibacterial effects of\n                      <jats:italic toggle=\"yes\">A. aureoles<\/jats:italic>\n                      GGNSJ001 are exerted. In summary, this study systematically illustrates how\n                      <jats:italic toggle=\"yes\">A. aureoles<\/jats:italic>\n                      GGNSJ001 activates ferritinophagy via the\n                      <jats:italic toggle=\"yes\">NCOA4\u2013FTH1<\/jats:italic>\n                      pathway, thereby enhancing oxidative stress and triggering ferroptosis to clear\n                      <jats:italic toggle=\"yes\">S. aureus<\/jats:italic>\n                      -infected macrophages. These findings offer novel mechanistic insights and a promising therapeutic strategy for combating antibiotic-resistant bacterial infections.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>IMPORTANCE<\/jats:title>\n                    <jats:p>\n                      This work addresses the critical challenge of antibiotic-resistant\n                      <jats:italic toggle=\"yes\">Staphylococcus aureus<\/jats:italic>\n                      infections by identifying a novel antifungal strategy. We demonstrate that a natural compound from the\n                      <jats:italic toggle=\"yes\">Aspergillus aureoles<\/jats:italic>\n                      GGNSJ001 can clear infected immune cells by hijacking a specific cell death pathway known as ferroptosis. This represents a paradigm shift, as it targets the host's cellular machinery to combat bacteria rather than the pathogen directly, offering a promising new avenue to overcome drug resistance. The findings provide a foundational framework for developing innovative host-directed therapies against persistent bacterial infections.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1128\/spectrum.03923-25","type":"journal-article","created":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T15:26:55Z","timestamp":1783006015000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":0,"title":["Mediating ferritinophagy and ferroptosis: a novel strategy against\n                    <i>Staphylococcus aureus<\/i>\n                    infection from a Kudzu root endophytic fungus"],"prefix":"10.1128","volume":"14","author":[{"given":"Wenshu","family":"Zou","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/042pgcv68","id-type":"ROR","asserted-by":"publisher"}],"name":"Jiangxi Province Key Laboratory of Sustainable Utilization of Traditional Chinese Medicine Resources, Institute of 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