{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T03:56:03Z","timestamp":1788926163644,"version":"build-2803163510"},"reference-count":41,"publisher":"American Society for Microbiology","issue":"11","license":[{"start":{"date-parts":[[2024,11,21]],"date-time":"2024-11-21T00:00:00Z","timestamp":1732147200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2024,11,21]],"date-time":"2024-11-21T00:00:00Z","timestamp":1732147200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/100000060","name":"HHS | NIH | National Institute of Allergy and Infectious Diseases","doi-asserted-by":"crossref","award":["1R01AI177604"],"award-info":[{"award-number":["1R01AI177604"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["mSphere"],"published-print":{"date-parts":[[2024,11,21]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:sec>\n            <jats:title\/>\n            <jats:p>\n              <jats:italic>Candida auris<\/jats:italic>\n              is an emerging multi-drug-resistant fungal pathogen that colonizes the skin and causes invasive infections in hospitalized patients. Multi-cellular aggregative phenotype is widely reported in the\n              <jats:italic>C. auris<\/jats:italic>\n              isolates, but its role in skin colonization and host immune response is not yet known. In this study, we generated aggregative phenotype by deleting the\n              <jats:italic>ACE2<\/jats:italic>\n              gene in\n              <jats:italic>C. auris<\/jats:italic>\n              and determined the fungal colonization and host immune response using an intradermal mouse model of\n              <jats:italic>C. auris<\/jats:italic>\n              skin infection. Our results indicate that mice infected with\n              <jats:italic>ace2<\/jats:italic>\n              \u0394 strain had significantly lower fungal load after 3 and 14 days post-infections compared to the non-aggregative wild-type and the\n              <jats:italic>ACE2<\/jats:italic>\n              reintegrated strain. The colonization of\n              <jats:italic>ace2<\/jats:italic>\n              \u0394 is associated with increased recruitment of CD11b\n              <jats:sup>+<\/jats:sup>\n              Ly6G\n              <jats:sup>+<\/jats:sup>\n              neutrophils and decreased accumulation of CD11b\n              <jats:sup>+<\/jats:sup>\n              Ly6 C\n              <jats:sup>hi<\/jats:sup>\n              inflammatory monocytes and CD11b\n              <jats:sup>+<\/jats:sup>\n              MHCII\n              <jats:sup>+<\/jats:sup>\n              CD64\n              <jats:sup>+<\/jats:sup>\n              macrophages. Furthermore, Th17 cells and type 3 innate lymphoid cells (ILCs) were significantly increased in the skin tissue of\n              <jats:italic>ace2<\/jats:italic>\n              \u0394 infected mice. Our findings suggest that aggregative phenotype mediated by\n              <jats:italic>ACE2<\/jats:italic>\n              deletion in\n              <jats:italic>C. auris<\/jats:italic>\n              induces potent neutrophil and IL-17-mediated immune response and reduces fungal colonization in the skin.\n            <\/jats:p>\n            <jats:sec>\n              <jats:title>IMPORTANCE<\/jats:title>\n              <jats:p>\n                <jats:italic>C. auris<\/jats:italic>\n                is a rapidly emerging fungal pathogen that can colonize hospitalized patients, especially in skin tissue, and cause invasive infections.\n                <jats:italic>C. auris<\/jats:italic>\n                isolates exhibit morphological heterogeneity, and the multicellular aggregative phenotype of\n                <jats:italic>C. auris<\/jats:italic>\n                is reported frequently in clinical settings. Understanding the role of fungal morphotypes in colonization, persistence, and immune response in the skin microenvironment will have potential applications in clinical diagnosis and novel preventive and therapeutic measures. Here, we utilized the murine model of intradermal infection and determined that the aggregative phenotype of\n                <jats:italic>C. auris<\/jats:italic>\n                as the result of\n                <jats:italic>ACE2<\/jats:italic>\n                gene deletion elicits potential innate and adaptive immune responses in mice. These observations will help explain the differences in the skin colonization and immune responses of the aggregative morphotype of\n                <jats:italic>C. auris<\/jats:italic>\n                and open the door to developing novel antifungal therapeutics.\n              <\/jats:p>\n            <\/jats:sec>\n          <\/jats:sec>","DOI":"10.1128\/msphere.00734-24","type":"journal-article","created":{"date-parts":[[2024,10,30]],"date-time":"2024-10-30T13:50:24Z","timestamp":1730296224000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":13,"title":["Cell aggregation mediated by\n            <i>ACE2<\/i>\n            deletion in\n            <i>Candida auris<\/i>\n            modulates fungal colonization and host immune responses in the skin"],"prefix":"10.1128","volume":"9","author":[{"given":"Abishek","family":"Balakumar","sequence":"first","affiliation":[{"name":"Department of Comparative Pathobiology, College of Veterinary Medicine, Purdue University, West Lafayette, Indiana, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2262-8168","authenticated-orcid":false,"given":"Abigail","family":"Cox","sequence":"additional","affiliation":[{"name":"Department of Comparative Pathobiology, College of Veterinary Medicine, Purdue University, West Lafayette, Indiana, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0031-2392","authenticated-orcid":true,"given":"Shankar","family":"Thangamani","sequence":"additional","affiliation":[{"name":"Department of Comparative Pathobiology, College of Veterinary Medicine, Purdue University, West Lafayette, Indiana, USA"},{"name":"Purdue Institute for Immunology, Inflammation and Infectious Diseases (PI4D), West Lafayette, Indiana, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.3201\/eid2907.230540"},{"key":"e_1_3_4_3_2","volume-title":"Antibiotic resistance threats in the United States, 2019. 2019","author":"CDC","year":"2019","unstructured":"CDC. 2019. 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