{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T13:45:52Z","timestamp":1791639952337,"version":"4.3.4"},"reference-count":77,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,8,22]],"date-time":"2025-08-22T00:00:00Z","timestamp":1755820800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Infect. Microbiol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Co-infections of\n                      <jats:italic>Candida albicans<\/jats:italic>\n                      and\n                      <jats:italic>Staphylococcus aureus<\/jats:italic>\n                      can significantly increase morbidity and mortality. However, the effect of\n                      <jats:italic>C. albicans\u2013S. aureus<\/jats:italic>\n                      co-existence on virulence factor secretion and pro-inflammatory effects remain elusive.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We systematically investigated the virulence factors released by\n                      <jats:italic>C.\u00a0albicans<\/jats:italic>\n                      and\n                      <jats:italic>S. aureus<\/jats:italic>\n                      under different culturing conditions using proteomics. We characterized their pro-inflammatory effects in macrophages with transcriptomics and gene set enrichment analysis.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results and Discussion<\/jats:title>\n                    <jats:p>\n                      We showed that co-culturing of\n                      <jats:italic>C. albicans<\/jats:italic>\n                      and\n                      <jats:italic>S. aureus<\/jats:italic>\n                      promoted the secretion of 7 cytolytic, 11 proteolytic, and 3 lipolytic extracellular virulence factors (ECVFs) and impacted non-ECVFs, owing to Als1\/Als3-mediated interactions, the presence of\n                      <jats:italic>C. albicans<\/jats:italic>\n                      , or its pH maintenance. Co-culturing promotes\n                      <jats:italic>C. albicans<\/jats:italic>\n                      hypha formation and \u03b2-glucan masking, suggesting that co-culturing enhances both\n                      <jats:italic>C. albicans<\/jats:italic>\n                      invasion and immune evasion. Moreover, the secretome of\n                      <jats:italic>C. albicans\u2013S. aureus<\/jats:italic>\n                      co-culture increased pro-inflammatory pathways including promoting TNF-, NFKB-, and Toll-like receptor signaling pathways, as well as cytokine\u2013cytokine receptor interactions in macrophages. Our findings support that\n                      <jats:italic>C. albicans<\/jats:italic>\n                      and\n                      <jats:italic>S. aureus<\/jats:italic>\n                      reciprocally promote their virulence potential and pro-inflammatory effects, which may provide mechanistic insights into the increased morbidity and mortality during their co-infection\n                      <jats:italic>in vivo<\/jats:italic>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fcimb.2025.1629373","type":"journal-article","created":{"date-parts":[[2025,8,22]],"date-time":"2025-08-22T05:27:30Z","timestamp":1755840450000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":12,"title":["Candida albicans and Staphylococcus aureus reciprocally promote their virulence factor secretion and pro-inflammatory effects"],"prefix":"10.3389","volume":"15","author":[{"given":"Raymond","family":"Pasman","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bastiaan P.","family":"Krom","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martijs J.","family":"Jonker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wim C.","family":"de Leeuw","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gertjan","family":"Kramer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stanley","family":"Brul","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sebastian A. 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