{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T11:52:43Z","timestamp":1785412363504,"version":"3.56.0"},"reference-count":52,"publisher":"American Society for Microbiology","issue":"4","license":[{"start":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T00:00:00Z","timestamp":1776816000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T00:00:00Z","timestamp":1776816000000},"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":["Appl Environ Microbiol"],"published-print":{"date-parts":[[2026,4,22]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      Interkingdom interactions between\n                      <jats:italic toggle=\"yes\">Candida albicans<\/jats:italic>\n                      and\n                      <jats:italic toggle=\"yes\">Staphylococcus aureus<\/jats:italic>\n                      promote lethal dissemination of the bacterium. During this process,\n                      <jats:italic toggle=\"yes\">C. albicans<\/jats:italic>\n                      hypha invasion aids\n                      <jats:italic toggle=\"yes\">S. aureus<\/jats:italic>\n                      dissemination through Als1p\/Als3p-facilitated co-invasion. The effects of\n                      <jats:italic toggle=\"yes\">S. aureus<\/jats:italic>\n                      on\n                      <jats:italic toggle=\"yes\">C. albicans<\/jats:italic>\n                      hypha formation and invasion are, however, unknown. In this study, we used both liquid mDMEM-DMP as well as a previously constructed semi-solid adaptation of the medium (mDMEM-DMPA) to study the effects of\n                      <jats:italic toggle=\"yes\">C. albicans\/S. aureus<\/jats:italic>\n                      co-culturing on hypha formation and invasion. Semi-solid-based co-culturing significantly increased colony size and generally increased hypha invasion. Liquid growth-based time-lapse microscopy showed that\n                      <jats:italic toggle=\"yes\">S. aureus<\/jats:italic>\n                      significantly promoted both\n                      <jats:italic toggle=\"yes\">C. albicans<\/jats:italic>\n                      hypha length and elongation rate. Further semi-solid-based growth results revealed that &gt;3 kDa-secreted\n                      <jats:italic toggle=\"yes\">S. aureus<\/jats:italic>\n                      factors were accountable for the increase in\n                      <jats:italic toggle=\"yes\">C. albicans<\/jats:italic>\n                      hypha growth. A newly constructed\n                      <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                      assay confirmed the co-invasion of\n                      <jats:italic toggle=\"yes\">S. aureus<\/jats:italic>\n                      during co-culturing and showed that deletion of\n                      <jats:italic toggle=\"yes\">C. albicans<\/jats:italic>\n                      Als1p\/Als3p abolished the co-invasion of\n                      <jats:italic toggle=\"yes\">S. aureus<\/jats:italic>\n                      during co-culturing. In conclusion, our study shows that\n                      <jats:italic toggle=\"yes\">S. aureus<\/jats:italic>\n                      affects\n                      <jats:italic toggle=\"yes\">C. albicans<\/jats:italic>\n                      virulence by actively stimulating\n                      <jats:italic toggle=\"yes\">C. albicans<\/jats:italic>\n                      hypha extension through the production of, presently unknown, secreted factors and sequentially using hypha proteins Als1p and Als3p to co-invade. Therefore,\n                      <jats:italic toggle=\"yes\">S. aureus<\/jats:italic>\n                      can stimulate\n                      <jats:italic toggle=\"yes\">C. albicans<\/jats:italic>\n                      epithelial invasion even prior to attaching to its hyphae, providing the foundation for subsequent co-invasion.\n                    <\/jats:p>\n                    <jats:sec>\n                      <jats:title>IMPORTANCE<\/jats:title>\n                      <jats:p>\n                        Epithelial barriers normally protect against invasion and systemic infection by\n                        <jats:italic toggle=\"yes\">S. aureus<\/jats:italic>\n                        , but frequently, such infections occur without a port of entry. One route of\n                        <jats:italic toggle=\"yes\">S. aureus<\/jats:italic>\n                        epithelial traversal is through co-invasion with the highly invasive\n                        <jats:italic toggle=\"yes\">Candida albicans<\/jats:italic>\n                        . Understanding this interaction in detail is of high importance in view of the prevention of these infections. Our study shows how the\n                        <jats:italic toggle=\"yes\">S. aureus<\/jats:italic>\n                        and C.\n                        <jats:italic toggle=\"yes\">albicans<\/jats:italic>\n                        interaction results in mutual benefit.\n                        <jats:italic toggle=\"yes\">S. aureus<\/jats:italic>\n                        appeared to affect\n                        <jats:italic toggle=\"yes\">C. albicans<\/jats:italic>\n                        virulence by actively stimulating\n                        <jats:italic toggle=\"yes\">C. albicans<\/jats:italic>\n                        hypha extension through the production of, presently unknown, secreted factors and sequentially using hypha proteins Als1p and Als3p to bind to the hyphae and co-invade. These insights are important from a microbial ecological perspective and offer important potential targets for interfering with the interaction and reducing the virulence of these opportunistic pathogens.\n                      <\/jats:p>\n                    <\/jats:sec>\n                  <\/jats:sec>","DOI":"10.1128\/aem.01961-25","type":"journal-article","created":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T13:01:29Z","timestamp":1774962089000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":0,"title":["Secreted factors of\n                    <i>Staphylococcus aureus<\/i>\n                    promote co-invasion with\n                    <i>Candida albicans<\/i>\n                    by inducing hypha formation and invasion"],"prefix":"10.1128","volume":"92","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-8518-5635","authenticated-orcid":true,"given":"Raymond","family":"Pasman","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/04dkp9463","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Molecular Biology and Microbial Food Safety, Swammerdam Institute for Life Sciences, University of Amsterdam","place":["Amsterdam, the Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1497-1161","authenticated-orcid":true,"given":"Bastiaan P.","family":"Krom","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/008xxew50","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Preventive Dentistry, Academic Centre for Dentistry Amsterdam, University of Amsterdam and Vrije Universiteit Amsterdam","place":["Amsterdam, the Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3526-4586","authenticated-orcid":true,"given":"Jianbo","family":"Zhang","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/04dkp9463","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Molecular Biology and Microbial Food Safety, Swammerdam Institute for Life Sciences, University of Amsterdam","place":["Amsterdam, the Netherlands"]},{"name":"Amsterdam Gastroenterology, Endocrinology and Metabolism, Amsterdam UMC, Location Academic Medical Center, Tytgat Institute for Liver and Intestinal Research","place":["Amsterdam, the Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5706-8768","authenticated-orcid":true,"given":"Stanley","family":"Brul","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/04dkp9463","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Molecular Biology and Microbial Food Safety, Swammerdam Institute for Life Sciences, University of Amsterdam","place":["Amsterdam, the Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9589-186X","authenticated-orcid":false,"given":"Sebastian A. 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