{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T11:42:53Z","timestamp":1788262973507,"version":"build-2803163510"},"reference-count":48,"publisher":"American Society for Microbiology","issue":"6","license":[{"start":{"date-parts":[[2018,6,1]],"date-time":"2018-06-01T00:00:00Z","timestamp":1527811200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/501100003762","name":"Institut Pasteur","doi-asserted-by":"crossref","award":["PTR468"],"award-info":[{"award-number":["PTR468"]}],"id":[{"id":"10.13039\/501100003762","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100003329","name":"Ministerio de Econom\u00eda y Competitividad","doi-asserted-by":"publisher","award":["SAF2013-48382-R"],"award-info":[{"award-number":["SAF2013-48382-R"]}],"id":[{"id":"10.13039\/501100003329","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2018,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            <jats:named-content content-type=\"genus-species\">Aspergillus fumigatus<\/jats:named-content>\n            can cause pulmonary aspergillosis in immunocompromised patients and is associated with a high mortality rate due to a lack of reliable treatment options. This opportunistic pathogen requires zinc in order to grow and cause disease. Novel compounds that interfere with fungal zinc metabolism may therefore be of therapeutic interest. We screened chemical libraries containing 59,223 small molecules using a resazurin assay that compared their effects on an\n            <jats:named-content content-type=\"genus-species\">A. fumigatus<\/jats:named-content>\n            wild-type strain grown under zinc-limiting conditions and on a zinc transporter knockout strain grown under zinc-replete conditions to identify compounds affecting zinc metabolism. After a first screen, 116 molecules were selected whose inhibitory effects on fungal growth were further tested by using luminescence assays and hyphal length measurements to confirm their activity, as well as by toxicity assays on HeLa cells and mice. Six compounds were selected following a rescreening, of which two were pyrazolones, two were porphyrins, and two were polyaminocarboxylates. All three groups showed good\n            <jats:italic>in vitro<\/jats:italic>\n            activity, but only one of the polyaminocarboxylates was able to significantly improve the survival of immunosuppressed mice suffering from pulmonary aspergillosis. This two-tier screening approach led us to the identification of a novel small molecule with\n            <jats:italic>in vivo<\/jats:italic>\n            fungicidal effects and low murine toxicity that may lead to the development of new treatment options for fungal infections by administration of this compound either as a monotherapy or as part of a combination therapy.\n          <\/jats:p>","DOI":"10.1128\/aac.02510-17","type":"journal-article","created":{"date-parts":[[2018,4,5]],"date-time":"2018-04-05T10:48:09Z","timestamp":1522925289000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":3,"title":["A Novel Polyaminocarboxylate Compound To Treat Murine Pulmonary Aspergillosis by Interfering with Zinc Metabolism"],"prefix":"10.1128","volume":"62","author":[{"given":"Paris","family":"Laskaris","sequence":"first","affiliation":[{"name":"Institut Pasteur, Cytokines &amp; Inflammation Unit, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roc\u00edo","family":"Vicentefranqueira","sequence":"additional","affiliation":[{"name":"Instituto de Biolog\u00eda Funcional y Gen\u00f3mica (IBFG), Departamento de Microbiolog\u00eda y Gen\u00e9tica, Universidad de Salamanca, Salamanca, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olivier","family":"Helynck","sequence":"additional","affiliation":[{"name":"Institut Pasteur, Chemistry and Biocatalysis Unit, CNRS UMR3523, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gr\u00e9gory","family":"Jouvion","sequence":"additional","affiliation":[{"name":"Institut Pasteur, Human Histopathology and Animal Models Unit, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9 Antonio","family":"Calera","sequence":"additional","affiliation":[{"name":"Instituto de Biolog\u00eda Funcional y Gen\u00f3mica (IBFG), Departamento de 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