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The increasing incidence of antifungal resistance underscores the urgent need for agents with novel mechanisms of action. APC6 is a zinc-chelating cyclic alkyl polyamine compound that selectively disrupts zinc homeostasis in fungal cells. We have previously reported that APC6 has antifungal activity against\n                      <jats:italic toggle=\"yes\">Candida<\/jats:italic>\n                      spp., including\n                      <jats:italic toggle=\"yes\">Candida auris<\/jats:italic>\n                      , and low cytotoxicity to human cells. In this study, we evaluated the\n                      <jats:italic toggle=\"yes\">in vivo<\/jats:italic>\n                      efficacy and safety of APC6 using a neutropenic murine model of disseminated\n                      <jats:italic toggle=\"yes\">C. auris<\/jats:italic>\n                      infection. APC6 significantly improved survival and reduced fungal burden in the liver, kidneys, and brain. At a therapeutic dose of 15 mg\/kg, APC6 had similar or superior antifungal activity to that of amphotericin B. Histopathological analysis revealed a decreased number of fungal microabscesses in APC6-treated tissues. No significant adverse effects were observed following 28-day repeated intraperitoneal administration, and the Ames assay revealed no mutagenic activity. To our knowledge, this is the first study to demonstrate that a zinc-chelating compound can improve survival and reduce organ fungal burden in a mammalian model of drug-resistant\n                      <jats:italic toggle=\"yes\">C. auris<\/jats:italic>\n                      infection. These results highlight APC6 as a promising lead compound targeting fungal zinc homeostasis and support its further development as a novel antifungal agent.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1128\/aac.00856-25","type":"journal-article","created":{"date-parts":[[2025,9,26]],"date-time":"2025-09-26T15:38:18Z","timestamp":1758901098000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":3,"title":["A zinc-chelating cyclic alkyl polyamine compound is efficient and safe in a murine model of multidrug-resistant\n                    <i>Candida auris<\/i>\n                    infection"],"prefix":"10.1128","volume":"69","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8804-0645","authenticated-orcid":true,"given":"Takayuki","family":"Shinohara","sequence":"first","affiliation":[{"name":"Department of Fungal Infection, National Institute of Infectious Diseases, Japan Institute for Health Security","place":["Tokyo, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3570-9100","authenticated-orcid":true,"given":"Akira","family":"Wada","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/023rffy11","id-type":"ROR","asserted-by":"publisher"}],"name":"Center for Integrative Medical Sciences, RIKEN","place":["Kanagawa, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6355-716X","authenticated-orcid":true,"given":"Masahiro","family":"Abe","sequence":"additional","affiliation":[{"name":"Department of Fungal Infection, National Institute of Infectious Diseases, Japan Institute for Health Security","place":["Tokyo, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sayoko","family":"Oiki","sequence":"additional","affiliation":[{"name":"Department of Fungal Infection, National Institute of Infectious Diseases, Japan Institute for Health Security","place":["Tokyo, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ami","family":"Koizumi","sequence":"additional","affiliation":[{"name":"Department of Fungal Infection, National Institute of Infectious Diseases, Japan Institute for Health Security","place":["Tokyo, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amato","family":"Otani","sequence":"additional","affiliation":[{"name":"Department of Fungal Infection, National Institute of Infectious Diseases, Japan Institute for Health Security","place":["Tokyo, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harutaka","family":"Katano","sequence":"additional","affiliation":[{"name":"Department of Infectious Disease Pathology, National Institute of Infectious Diseases, Japan Institute for Health Security","place":["Tokyo, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8942-0869","authenticated-orcid":true,"given":"Yoshitsugu","family":"Miyazaki","sequence":"additional","affiliation":[{"name":"Department of Fungal Infection, National Institute of Infectious Diseases, Japan Institute for Health Security","place":["Tokyo, Japan"]},{"name":"Leprosy Research Center, National Institute of Infectious Diseases, Japan Institute for Health Security","place":["Tokyo, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_5_2_2","doi-asserted-by":"publisher","DOI":"10.2165\/00003495-200161001-00001"},{"key":"e_1_3_5_3_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jix131"},{"key":"e_1_3_5_4_2","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2018.01656"},{"key":"e_1_3_5_5_2","doi-asserted-by":"publisher","DOI":"10.1002\/mbo3.578"},{"key":"e_1_3_5_6_2","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciw691"},{"key":"e_1_3_5_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/S2666-5247(24)00042-9"},{"key":"e_1_3_5_8_2","doi-asserted-by":"publisher","DOI":"10.1093\/mmy\/myz012"},{"key":"e_1_3_5_9_2","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2019.00181"},{"key":"e_1_3_5_10_2","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2020.574736"},{"key":"e_1_3_5_11_2","doi-asserted-by":"publisher","DOI":"10.1128\/aac.00003-23"},{"key":"e_1_3_5_12_2","doi-asserted-by":"publisher","DOI":"10.1093\/femsre\/fux050"},{"key":"e_1_3_5_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.heliyon.2021.e07805"},{"key":"e_1_3_5_14_2","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2015.00160"},{"key":"e_1_3_5_15_2","doi-asserted-by":"publisher","DOI":"10.1023\/a:1012976615056"},{"key":"e_1_3_5_16_2","first-page":"2391","article-title":"N-methyl-D-aspartate (NMDA)--induced apoptosis in rat retina","volume":"40","author":"Lam TT","year":"1999","unstructured":"Lam TT, Abler AS, Kwong JMK, Tso MOM. 1999. 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