{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T17:45:50Z","timestamp":1780508750894,"version":"3.54.1"},"reference-count":25,"publisher":"American Society for Microbiology","issue":"4","license":[{"start":{"date-parts":[[2024,4,2]],"date-time":"2024-04-02T00:00:00Z","timestamp":1712016000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2024,4,2]],"date-time":"2024-04-02T00:00:00Z","timestamp":1712016000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"name":"Canadian Government | Canadian Institutes of Health Research","award":["FDN-154288"],"award-info":[{"award-number":["FDN-154288"]}]},{"name":"HHS | National Institutes of Health","award":["U01 TR002625"],"award-info":[{"award-number":["U01 TR002625"]}]},{"name":"HHS | National Institutes of Health","award":["R35 GM 118173"],"award-info":[{"award-number":["R35 GM 118173"]}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Microbiol Spectr"],"published-print":{"date-parts":[[2024,4,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:sec>\n            <jats:title\/>\n            <jats:p>\n              <jats:italic>Candida albicans<\/jats:italic>\n              , one of the most prevalent human fungal pathogens, causes diverse diseases extending from superficial infections to deadly systemic mycoses. Currently, only three major classes of antifungal drugs are available to treat systemic infections: azoles, polyenes, and echinocandins. Alarmingly, the efficacy of these antifungals against\n              <jats:italic>C. albicans<\/jats:italic>\n              is hindered both by basal tolerance toward the drugs and the development of resistance mechanisms such as alterations of the drug\u2019s target, modulation of stress responses, and overexpression of efflux pumps. Thus, the need to identify novel antifungal strategies is dire. To address this challenge, we screened 3,049 structurally-diverse compounds from the Boston University Center for Molecular Discovery (BU-CMD) chemical library against a\n              <jats:italic>C. albicans<\/jats:italic>\n              clinical isolate and identified 17 molecules that inhibited\n              <jats:italic>C. albicans<\/jats:italic>\n              growth by &gt;80% relative to controls. Among the most potent compounds were CMLD013360, CMLD012661, and CMLD012693, molecules representing two distinct chemical scaffolds, including 3-hydroxyquinolinones and a xanthone natural product. Based on structural insights, CMLD013360, CMLD012661, and CMLD012693 were hypothesized to exert antifungal activity through metal chelation. Follow-up investigations revealed all three compounds exerted antifungal activity against non-albicans\n              <jats:italic>Candida<\/jats:italic>\n              , including\n              <jats:italic>Candida auris<\/jats:italic>\n              and\n              <jats:italic>Candida glabrata<\/jats:italic>\n              , with the xanthone natural product CMLD013360 also displaying activity against the pathogenic mould\n              <jats:italic>Aspergillus fumigatus<\/jats:italic>\n              . Media supplementation with metallonutrients, namely ferric or ferrous iron, rescued\n              <jats:italic>C. albicans<\/jats:italic>\n              growth, confirming these compounds act as metal chelators. Thus, this work identifies and characterizes two chemical scaffolds that chelate iron to inhibit the growth of the clinically relevant fungal pathogen\n              <jats:italic>C. albicans<\/jats:italic>\n            <\/jats:p>\n            <jats:sec>\n              <jats:title>IMPORTANCE<\/jats:title>\n              <jats:p>\n                The worldwide incidence of invasive fungal infections is increasing at an alarming rate. Systemic candidiasis caused by the opportunistic pathogen\n                <jats:italic>Candida albicans<\/jats:italic>\n                is the most common cause of life-threatening fungal infection. However, due to the limited number of antifungal drug classes available and the rise of antifungal resistance, an urgent need exists for the identification of novel treatments. By screening a compound collection from the Boston University Center for Molecular Discovery (BU-CMD), we identified three compounds representing two distinct chemical scaffolds that displayed activity against\n                <jats:italic>C. albicans<\/jats:italic>\n                . Follow-up analyses confirmed these molecules were also active against other pathogenic fungal species including\n                <jats:italic>Candida auris<\/jats:italic>\n                and\n                <jats:italic>Aspergillus fumigatus<\/jats:italic>\n                . Finally, we determined that these compounds inhibit the growth of\n                <jats:italic>C. albicans<\/jats:italic>\n                in culture through iron chelation. Overall, this observation describes two novel chemical scaffolds with antifungal activity against diverse fungal pathogens.\n              <\/jats:p>\n            <\/jats:sec>\n          <\/jats:sec>","DOI":"10.1128\/spectrum.04095-23","type":"journal-article","created":{"date-parts":[[2024,2,20]],"date-time":"2024-02-20T14:35:17Z","timestamp":1708439717000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":10,"title":["A chemical screen identifies structurally diverse metal chelators with activity against the fungal pathogen\n            <i>Candida albicans<\/i>"],"prefix":"10.1128","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-1755-2656","authenticated-orcid":false,"given":"Sara","family":"Fallah","sequence":"first","affiliation":[{"name":"Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dustin","family":"Duncan","sequence":"additional","affiliation":[{"name":"Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada"},{"name":"Department of Chemistry, Brock University, St. Catharines, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyle D.","family":"Reichl","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Center for Molecular Discovery (BU-CMD), Boston University, Boston, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael J.","family":"Smith","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Center for Molecular Discovery (BU-CMD), Boston University, Boston, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenyu","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Center for Molecular Discovery (BU-CMD), Boston University, Boston, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"Jr.","given":"John A.","family":"Porco","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Center for Molecular Discovery (BU-CMD), Boston University, Boston, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lauren E.","family":"Brown","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Center for Molecular Discovery (BU-CMD), Boston University, Boston, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luke","family":"Whitesell","sequence":"additional","affiliation":[{"name":"Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5797-0110","authenticated-orcid":false,"given":"Nicole","family":"Robbins","sequence":"additional","affiliation":[{"name":"Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5797-0110","authenticated-orcid":false,"given":"Leah E.","family":"Cowen","sequence":"additional","affiliation":[{"name":"Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.3004404"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0169-409X(96)00423-1"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jnatprod.5b00947"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1021\/jm901137j"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.5b00361"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.8b00686"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.03329-19"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-20183-3"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1000532"},{"key":"e_1_3_3_11_2","volume-title":"Syntheses of griffipavixanthone and related dimeric xanthones using para-quinone methides","author":"Smith MJ","year":"2021","unstructured":"Smith MJ. 2021. Syntheses of griffipavixanthone and related dimeric xanthones using para-quinone methides. Doctor of Philosophy. Boston University."},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1002\/chem.201602953"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1462-2920.2006.01025.x"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1155\/2022\/4911205"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.21769\/BioProtoc.252"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1128\/mbio.02730-22"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.2174\/1570163816666190227231437"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1006350"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.4103\/idoj.IDOJ_29_19"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10534-011-9451-4"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro2836"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1023\/a:1020259021641"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.mib.2013.09.006"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1002\/cbdv.202000442"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1010283"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1128\/EC.00158-10"}],"container-title":["Microbiology Spectrum"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/spectrum.04095-23","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/spectrum.04095-23","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,4,2]],"date-time":"2024-04-02T14:18:09Z","timestamp":1712067489000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/spectrum.04095-23"}},"subtitle":[],"editor":[{"given":"James B.","family":"Konopka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2024,4,2]]},"references-count":25,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2024,4,2]]}},"alternative-id":["10.1128\/spectrum.04095-23"],"URL":"https:\/\/doi.org\/10.1128\/spectrum.04095-23","relation":{},"ISSN":["2165-0497"],"issn-type":[{"value":"2165-0497","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,4,2]]},"assertion":[{"value":"2023-12-02","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-01-25","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-02-20","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e04095-23"}}