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Here we explored the fungal, host, and environmental factors that influence the ability of\n                      <jats:italic toggle=\"yes\">C. albicans<\/jats:italic>\n                      to colonize the mouse GI tract using a representative clinical strain, CLCA10. After a single gavage challenge (5 \u00d7 10\n                      <jats:sup>6<\/jats:sup>\n                      CFU\n                      <jats:italic toggle=\"yes\">C<\/jats:italic>\n                      .\n                      <jats:italic toggle=\"yes\">albicans<\/jats:italic>\n                      ), specific pathogen-free (SPF) mice remained colonized with\n                      <jats:italic toggle=\"yes\">C. albicans<\/jats:italic>\n                      strain CLCA10\n                      <jats:italic toggle=\"yes\">,<\/jats:italic>\n                      but not other\n                      <jats:italic toggle=\"yes\">Candida<\/jats:italic>\n                      species, for at least 58 days with the fungus confined largely to the gut luminal contents. Colonized mice exhibited no weight loss or other signs of active infection, and CLCA10 did not disrupt the gut microbiome. Moreover,\n                      <jats:italic toggle=\"yes\">C. albicans<\/jats:italic>\n                      colonization with CLCA10 was not substantially affected by the mouse commercial source or the method used to cultivate the fungus prior to gavage. Although some genetically manipulated\n                      <jats:italic toggle=\"yes\">C. albicans<\/jats:italic>\n                      strains were unable to robustly colonize, strain SC5314 also colonized the mouse gut despite having enhanced pathogenicity.\n                      <jats:italic toggle=\"yes\">C. albicans<\/jats:italic>\n                      CLCA10 gut colonization in part depended on the hypha-associated adhesins Als3 and Hwp1 and the peptide toxin candidalysin and could not be eradicated by potent antifungal therapy. Thus, this study concludes that\n                      <jats:italic toggle=\"yes\">C. albicans<\/jats:italic>\n                      gut colonization in the mouse is critically dependent on fungal hyphal factors, the targeting of which could enhance strategies to reduce\n                      <jats:italic toggle=\"yes\">C. albicans<\/jats:italic>\n                      gut colonization and the intractable threat to human health it represents.\n                    <\/jats:p>\n                    <jats:sec>\n                      <jats:title>IMPORTANCE<\/jats:title>\n                      <jats:p>\n                        <jats:italic toggle=\"yes\">Candida albicans<\/jats:italic>\n                        is an important human fungal pathogen and a ubiquitous colonizer of the gastrointestinal (GI) tract. However, it is not understood how\n                        <jats:italic toggle=\"yes\">C. albicans<\/jats:italic>\n                        persists within the GI tract and from which it may disperse to cause disease. Here, we demonstrated that multiple strains of\n                        <jats:italic toggle=\"yes\">C. albicans<\/jats:italic>\n                        , including the widely used SC5314 strain, robustly colonize the mouse GI tract for at least 2 months. This colonization caused no disruption to the host tissue or bacterial microbiome and was resistant to clearance by antifungal drugs. Importantly, colonization was mediated by proteins expressed by\n                        <jats:italic toggle=\"yes\">C. albicans<\/jats:italic>\n                        that are known to be involved in fungal virulence and unrelated to experimental conditions. Overall, this work identifies mechanisms by which\n                        <jats:italic toggle=\"yes\">C. albicans<\/jats:italic>\n                        persists in the GI tract, enhancing our knowledge of host-fungal interactions during commensal colonization and potentially how to reduce such colonization.\n                      <\/jats:p>\n                    <\/jats:sec>\n                  <\/jats:sec>","DOI":"10.1128\/spectrum.00567-25","type":"journal-article","created":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T13:00:22Z","timestamp":1753880422000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":10,"title":["Commensal colonization of\n                    <i>Candida albicans<\/i>\n                    in the mouse gastrointestinal tract is mediated via expression of candidalysin and adhesins"],"prefix":"10.1128","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5985-4148","authenticated-orcid":true,"given":"Kelsey E.","family":"Mauk","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02pttbw34","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Medicine, Baylor College of Medicine","place":["Houston, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6867-7697","authenticated-orcid":true,"given":"Pedro","family":"Miram\u00f3n","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03gds6c39","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Microbiology and Molecular Genetics, McGovern Medical School, The University of Texas Health Science Center at Houston","place":["Houston, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7881-8027","authenticated-orcid":true,"given":"Michael C.","family":"Lorenz","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03gds6c39","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Microbiology and Molecular Genetics, McGovern Medical School, The University of Texas Health Science Center at Houston","place":["Houston, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-6221-7763","authenticated-orcid":true,"given":"L\u00e9a","family":"Lortal","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/0220mzb33","id-type":"ROR","asserted-by":"publisher"}],"name":"Centre for Host-Microbiome Interactions, Faculty of Dentistry, Oral & Craniofacial Sciences, King\u2019s College London","place":["London, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8072-7917","authenticated-orcid":true,"given":"Julian R.","family":"Naglik","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/0220mzb33","id-type":"ROR","asserted-by":"publisher"}],"name":"Centre for Host-Microbiome Interactions, Faculty of Dentistry, Oral & Craniofacial Sciences, King\u2019s College London","place":["London, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6028-0425","authenticated-orcid":true,"given":"Bernhard","family":"Hube","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/055s37c97","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Microbial Pathogenicity Mechanisms, Leibniz Institute for Natural Product Research and Infection Biology, Hans Knoll Institute (HKI)","place":["Jena, Germany"]},{"id":[{"id":"https:\/\/ror.org\/05qpz1x62","id-type":"ROR","asserted-by":"publisher"}],"name":"Cluster of Excellence Balance of the Microverse, Friedrich Schiller University Jena","place":["Jena, Germany"]},{"id":[{"id":"https:\/\/ror.org\/00yd0p282","id-type":"ROR","asserted-by":"publisher"}],"name":"Institute of Microbiology, Friedrich Schiller University Jena","place":["Jena, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7473-9698","authenticated-orcid":false,"given":"Lynn","family":"Bimler","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02pttbw34","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Medicine, Baylor College of Medicine","place":["Houston, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Farrah","family":"Kheradmand","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02pttbw34","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Medicine, Baylor College of Medicine","place":["Houston, USA"]},{"id":[{"id":"https:\/\/ror.org\/02pttbw34","id-type":"ROR","asserted-by":"publisher"}],"name":"Dan L. 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