{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T12:29:10Z","timestamp":1785414550436,"version":"3.56.0"},"reference-count":44,"publisher":"American Society for Microbiology","issue":"5","license":[{"start":{"date-parts":[[2026,5,6]],"date-time":"2026-05-06T00:00:00Z","timestamp":1778025600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,5,6]],"date-time":"2026-05-06T00:00:00Z","timestamp":1778025600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82102454"],"award-info":[{"award-number":["82102454"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2026,5,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      <jats:italic toggle=\"yes\">Candida albicans<\/jats:italic>\n                      , a World Health Organization critical-priority fungal pathogen, represents the predominant cause of candidemia. Therapeutic failure is sometimes driven by antifungal tolerance, a phenotype distinct from resistance, whose underlying mechanisms remain incompletely defined. Here, we identify the peroxisomal protein Pex8 as a key regulator of tolerance to both azoles and amphotericin B. Although neither deletion nor overexpression of\n                      <jats:italic toggle=\"yes\">PEX8<\/jats:italic>\n                      altered minimum inhibitory concentrations, both modifications significantly reduced drug tolerance, as demonstrated by reduced fractional growth (FoG\n                      <jats:sub>20<\/jats:sub>\n                      ) and impaired survival under drug pressure. RNA-seq analysis showed that\n                      <jats:italic toggle=\"yes\">PEX8<\/jats:italic>\n                      overexpression leads to downregulation of ergosterol biosynthesis genes and remodeling of stress-response pathways, suggesting a possible transcriptional basis for the loss of azole tolerance. Complementary lipidomic profiling demonstrated that\n                      <jats:italic toggle=\"yes\">PEX8<\/jats:italic>\n                      genetic manipulations induce extensive membrane lipid remodeling, characterized by specific alterations in ceramide and lysophospholipid subclasses, thereby revealing an ergosterol-independent mechanism underlying amphotericin B tolerance attenuation. Phenotypically,\n                      <jats:italic toggle=\"yes\">PEX8<\/jats:italic>\n                      overexpression attenuated serum-induced hyphal morphogenesis and reduced virulence in a\n                      <jats:italic toggle=\"yes\">Galleria mellonella<\/jats:italic>\n                      infection model, consistent with downregulation of hyphal-associated and virulence-related genes. Our findings establish Pex8 as a central coordinator of oxidative stress adaptation, membrane homeostasis, filamentation, and pathogenicity, revealing a promising target for combating antifungal tolerance.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1128\/aac.01662-25","type":"journal-article","created":{"date-parts":[[2026,3,24]],"date-time":"2026-03-24T14:38:55Z","timestamp":1774363135000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":1,"title":["Peroxin Pex8 couples stress responses, antifungal tolerance, and virulence regulation in\n                    <i>Candida albicans<\/i>"],"prefix":"10.1128","volume":"70","author":[{"given":"Bangsheng","family":"Xi","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/05wbpaf14","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Laboratory Medicine, The First Affiliated Hospital of Wannan Medical College 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