{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T11:03:42Z","timestamp":1785409422384,"version":"3.56.0"},"posted":{"date-parts":[[2025,6,2]]},"group-title":"Microbiology","reference-count":34,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,6,2]],"date-time":"2025-06-02T00:00:00Z","timestamp":1748822400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nd\/4.0\/"}],"funder":[{"award":["U19 AI181767"],"award-info":[{"award-number":["U19 AI181767"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]},{"award":["P30 AR069620"],"award-info":[{"award-number":["P30 AR069620"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000861","name":"Burroughs Wellcome Fund","doi-asserted-by":"crossref","award":["1173374"],"award-info":[{"award-number":["1173374"]}],"id":[{"id":"10.13039\/100000861","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,10,31]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  <jats:italic>Candidozyma auris<\/jats:italic>\n                  is a growing public health concern, capable of causing long-term contamination of healthcare settings, skin colonization, and life-threatening bloodstream infections. However,\n                  <jats:italic>C. auris<\/jats:italic>\n                  pathogenesis is not well understood, which is exacerbated by limitations and discrepancies in existing animal infection models. Further, the effects of\n                  <jats:italic>C. auris<\/jats:italic>\n                  growth phase on virulence have not been examined, despite growth phase being linked to virulence in many bacterial species. To address this question, and to develop an immunocompetent murine model of infection, we directly compared log and stationary phase\n                  <jats:italic>C. auris<\/jats:italic>\n                  systemic infection in immunocompetent C57BL\/6J mice at high and low doses of infection. Systemic infection with high dose log phase\n                  <jats:italic>C. auris<\/jats:italic>\n                  results in rapid mortality between 2 hours and 1 day post infection, whereas stationary phase\n                  <jats:italic>C. auris<\/jats:italic>\n                  results in significantly extended survival. However, at low doses of infection, there was no difference in mortality kinetics between log and stationary phase cells. We observed that\n                  <jats:italic>C. auris<\/jats:italic>\n                  initially colonizes multiple organs but is rapidly cleared from the lungs and spleen, while kidney fungal burdens remain stable. Mice infected with high dose log phase\n                  <jats:italic>C. auris<\/jats:italic>\n                  had Fibrin-associated blood clotting in multiple organs and decreased serum Fibrinogen levels, suggesting that coagulation may drive rapid mortality. This was associated with increased \u03b2-glucan exposure and mannan abundance in log phase\n                  <jats:italic>C. auris<\/jats:italic>\n                  . These results will inform the development of a more standardized animal model of systemic\n                  <jats:italic>C. auris<\/jats:italic>\n                  infection, which can be used to reveal key aspects of\n                  <jats:italic>C. auris<\/jats:italic>\n                  pathogenesis.\n                <\/jats:p>\n                <jats:sec>\n                  <jats:title>Importance<\/jats:title>\n                  <jats:p>\n                    Despite its growing medical importance, there is limited understanding of\n                    <jats:italic>Candidozyma auris<\/jats:italic>\n                    pathogenesis, due in part to limitations of existing laboratory models of infection. To develop a more complete understanding of factors that contribute to\n                    <jats:italic>C. auris<\/jats:italic>\n                    pathogenesis, it will be necessary to establish consistent parameters for animal models of infection. To address this need, we directly compared log and stationary growth phases on\n                    <jats:italic>C. auris<\/jats:italic>\n                    pathogenesis in immunocompetent C57BL\/6J mice using a single virulent Clade I isolate. At a high dose of infection, host survival was dramatically different between log or stationary phase\n                    <jats:italic>C. auris<\/jats:italic>\n                    , suggesting that growth phase can affect\n                    <jats:italic>C. auris<\/jats:italic>\n                    pathogenesis. These differences correlated with increased exposure of pathogen-associated molecular patterns in the\n                    <jats:italic>C. auris<\/jats:italic>\n                    cell wall in log phase cells. These results will be instrumental in the future development of standardized animal models to study\n                    <jats:italic>C. auris<\/jats:italic>\n                    pathogenesis.\n                  <\/jats:p>\n                <\/jats:sec>","DOI":"10.1101\/2025.06.02.657403","type":"posted-content","created":{"date-parts":[[2025,6,3]],"date-time":"2025-06-03T01:30:16Z","timestamp":1748914216000},"source":"Crossref","is-referenced-by-count":0,"title":["Growth phase influences virulence in\n                  <i>Candidozyma auris<\/i>\n                  systemic infection models"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0303-6968","authenticated-orcid":false,"given":"Michael J.","family":"McFadden","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology, University of Michigan, Ann Arbor, MI 48109, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-0112-8379","authenticated-orcid":false,"given":"Juliet A.E.","family":"Anku","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Michigan, Ann Arbor, MI 48109, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8456-621X","authenticated-orcid":false,"given":"Faith A.","family":"Davis","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Michigan, Ann Arbor, MI 48109, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine","family":"Luke","sequence":"additional","affiliation":[{"name":"Section of Vascular Surgery, Department of Surgery, University of Michigan, Ann Arbor, MI 48109, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7613-2366","authenticated-orcid":false,"given":"Andrea","family":"Obi","sequence":"additional","affiliation":[{"name":"Section of Vascular Surgery, Department of Surgery, University of Michigan, Ann Arbor, MI 48109, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8901-0154","authenticated-orcid":false,"given":"Teresa R.","family":"O\u2019Meara","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Michigan, Ann Arbor, MI 48109, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026041200365278000_2025.06.02.657403v2.1","doi-asserted-by":"crossref","unstructured":"Ortiz-Roa C , Valderrama-Rios MC , Sierra-Uma\u00f1a SF , Rodr\u00edguez JY , Mu\u00f1et\u00f3n-L\u00f3pez GA , Sol\u00f3rzano-Ramos CA , Escand\u00f3n P , Alvarez-Moreno CA , Cort\u00e9s JA . 2023. Mortality caused by Candida auris bloodstream infections in comparison with other Candida species, a multicentre retrospective cohort. J Fungi (Basel) 9.","DOI":"10.3390\/jof9070715"},{"key":"2026041200365278000_2025.06.02.657403v2.2","doi-asserted-by":"crossref","unstructured":"Kim HY PhD , Nguyen TA MSc , Kidd S PhD , Chambers J MD , Alastruey-Izquierdo A PhD , Shin J-HMD , Dao A PhD , Forastiero A MD , Wahyuningsih R MD , Chakrabarti A MD , Beyer P , Gigante V PhD , Beardsley J PhD , Sati H PhD , Morrissey CO PhD , Alffenaar J-W PhD . 2024. Candida auris-a systematic review to inform the world health organization fungal priority pathogens list. Med Mycol 62.","DOI":"10.1093\/mmy\/myae042"},{"key":"2026041200365278000_2025.06.02.657403v2.3","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-31201-x"},{"key":"2026041200365278000_2025.06.02.657403v2.4","doi-asserted-by":"crossref","unstructured":"Xin H , Mohiuddin F , Tran J , Adams A , Eberle K. 2019. Experimental mouse models of disseminated Candida auris infection. mSphere 4.","DOI":"10.1128\/mSphere.00339-19"},{"key":"2026041200365278000_2025.06.02.657403v2.5","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-med-061523-021233"},{"key":"2026041200365278000_2025.06.02.657403v2.6","doi-asserted-by":"publisher","DOI":"10.1126\/science.adf8972"},{"key":"2026041200365278000_2025.06.02.657403v2.7","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-20183-3"},{"key":"2026041200365278000_2025.06.02.657403v2.8","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1007460"},{"key":"2026041200365278000_2025.06.02.657403v2.9","doi-asserted-by":"crossref","first-page":"5673","DOI":"10.1038\/s41467-025-60876-1","article-title":"Adhesin Als4112 promotes Candida auris skin colonization through interactions with keratinocytes and extracellular matrix proteins","volume":"16","year":"2025","journal-title":"Nat Commun"},{"key":"2026041200365278000_2025.06.02.657403v2.10","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-0716-2417-3_25"},{"key":"2026041200365278000_2025.06.02.657403v2.11","doi-asserted-by":"crossref","unstructured":"Torres SR , Pichowicz A , Torres-Velez F , Song R , Singh N , Lasek-Nesselquist E , De Jesus M. 2020. Impact of Candida auris Infection in a Neutropenic Murine Model. Antimicrob Agents Chemother 64.","DOI":"10.1128\/AAC.01625-19"},{"key":"2026041200365278000_2025.06.02.657403v2.12","doi-asserted-by":"publisher","DOI":"10.1111\/myc.12754"},{"key":"2026041200365278000_2025.06.02.657403v2.13","first-page":"93","article-title":"The first isolate of Candida auris in China: clinical and biological aspects","volume":"7","year":"2018","journal-title":"Emerg Microbes Infect"},{"key":"2026041200365278000_2025.06.02.657403v2.14","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1012011"},{"key":"2026041200365278000_2025.06.02.657403v2.15","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2958.1999.01519.x"},{"key":"2026041200365278000_2025.06.02.657403v2.16","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.micro.57.030502.090803"},{"key":"2026041200365278000_2025.06.02.657403v2.17","doi-asserted-by":"publisher","DOI":"10.1099\/00221287-144-7-1823"},{"key":"2026041200365278000_2025.06.02.657403v2.18","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2958.2003.03726.x"},{"key":"2026041200365278000_2025.06.02.657403v2.19","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra1208623"},{"key":"2026041200365278000_2025.06.02.657403v2.20","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-030-58971-4_15"},{"key":"2026041200365278000_2025.06.02.657403v2.21","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2567.2009.03200.x"},{"key":"2026041200365278000_2025.06.02.657403v2.22","doi-asserted-by":"crossref","first-page":"1516","DOI":"10.1038\/s41564-020-0780-3","article-title":"Transcriptional and functional insights into the host immune response against the emerging fungal pathogen Candida auris","volume":"5","year":"2020","journal-title":"Nat Microbiol"},{"key":"2026041200365278000_2025.06.02.657403v2.23","doi-asserted-by":"publisher","DOI":"10.1016\/0014-5793(80)81041-6"},{"key":"2026041200365278000_2025.06.02.657403v2.24","doi-asserted-by":"crossref","unstructured":"Wilhelm G , Mertowska P , Mertowski S , Przysucha A , Stru\u017cyna J , Grywalska E , Torres K. 2023. The Crossroads of the coagulation system and the immune system: Interactions and connections. Int J Mol Sci 24.","DOI":"10.3390\/ijms241612563"},{"key":"2026041200365278000_2025.06.02.657403v2.25","doi-asserted-by":"publisher","DOI":"10.1038\/nri3897"},{"key":"2026041200365278000_2025.06.02.657403v2.26","doi-asserted-by":"crossref","first-page":"508","DOI":"10.1177\/000313480206800602","article-title":"Human vascular endothelial cells express pattern recognition receptors for fungal glucans which stimulates nuclear factor kappaB activation and interleukin 8 production. Winner of the Best Paper Award from the Gold Medal Forum","volume":"68","year":"2002","journal-title":"Am Surg"},{"key":"2026041200365278000_2025.06.02.657403v2.27","doi-asserted-by":"publisher","DOI":"10.1086\/589516"},{"key":"2026041200365278000_2025.06.02.657403v2.28","doi-asserted-by":"publisher","DOI":"10.1016\/s0140-6736(64)91984-1"},{"key":"2026041200365278000_2025.06.02.657403v2.29","doi-asserted-by":"publisher","DOI":"10.1159\/000321157"},{"key":"2026041200365278000_2025.06.02.657403v2.30","doi-asserted-by":"publisher","DOI":"10.1186\/s12879-019-3999-y"},{"key":"2026041200365278000_2025.06.02.657403v2.31","doi-asserted-by":"publisher","DOI":"10.1128\/aac.00053-22"},{"key":"2026041200365278000_2025.06.02.657403v2.32","doi-asserted-by":"crossref","first-page":"3253","DOI":"10.1038\/s41598-023-30149-2","article-title":"Experimental venous thrombus resolution is driven by IL-6 mediated monocyte actions","volume":"13","year":"2023","journal-title":"Sci Rep"},{"key":"2026041200365278000_2025.06.02.657403v2.33","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-17204-5"},{"key":"2026041200365278000_2025.06.02.657403v2.34","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.2019"}],"container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1101\/2025.06.02.657403","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T05:02:31Z","timestamp":1782277351000},"score":1,"resource":{"primary":{"URL":"http:\/\/biorxiv.org\/lookup\/doi\/10.1101\/2025.06.02.657403"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,6,2]]},"references-count":34,"URL":"https:\/\/doi.org\/10.1101\/2025.06.02.657403","relation":{"is-preprint-of":[{"id-type":"doi","id":"10.1128\/msphere.00767-25","asserted-by":"subject"}]},"subject":[],"published":{"date-parts":[[2025,6,2]]},"subtype":"preprint"}}