{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,31]],"date-time":"2025-10-31T14:09:14Z","timestamp":1761919754068},"reference-count":56,"publisher":"American Society for Microbiology","issue":"1","license":[{"start":{"date-parts":[[2014,1,1]],"date-time":"2014-01-01T00:00:00Z","timestamp":1388534400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2014,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Human fungal infections represent a therapeutic challenge. Although effective strategies for treatment are available, resistance is spreading, and many therapies have unacceptable side effects. A clear need for novel antifungal targets and molecules is thus emerging. Here, we present the identification and characterization of the plant-derived diyne-furan fatty acid EV-086 as a novel antifungal compound. EV-086 has potent and broad-spectrum activity\n            <jats:italic>in vitro<\/jats:italic>\n            against\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Candida<\/jats:named-content>\n            ,\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Aspergillus<\/jats:named-content>\n            , and\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Trichophyton<\/jats:named-content>\n            spp., whereas activities against bacteria and human cell lines are very low. Chemical-genetic profiling of\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Saccharomyces cerevisiae<\/jats:named-content>\n            deletion mutants identified lipid metabolic processes and organelle organization and biogenesis as targets of EV-086. Pathway modeling suggested that EV-086 inhibits delta-9 fatty acid desaturation, an essential process in\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">S. cerevisiae<\/jats:named-content>\n            , depending on the delta-9 fatty acid desaturase\n            <jats:italic>OLE1<\/jats:italic>\n            . Delta-9 unsaturated fatty acids\u2014but not saturated fatty acids\u2014antagonized the EV-086-mediated growth inhibition, and transcription of the\n            <jats:italic>OLE1<\/jats:italic>\n            gene was strongly upregulated in the presence of EV-086. EV-086 increased the ratio of saturated to unsaturated free fatty acids and phosphatidylethanolamine fatty acyl chains, respectively. Furthermore, EV-086 was rapidly taken up into the lipid fraction of the cell and incorporated into phospholipids. Together, these findings demonstrate that EV-086 is an inhibitor of delta-9 fatty acid desaturation and that the mechanism of inhibition might involve an EV-086\u2013phospholipid. Finally, EV-086 showed efficacy in a guinea pig skin dermatophytosis model of topical\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Trichophyton<\/jats:named-content>\n            infection, which demonstrates that delta-9 fatty acid desaturation is a valid antifungal target, at least for dermatophytoses.\n          <\/jats:p>","DOI":"10.1128\/aac.01443-13","type":"journal-article","created":{"date-parts":[[2013,11,5]],"date-time":"2013-11-05T04:07:25Z","timestamp":1383624445000},"page":"455-466","update-policy":"http:\/\/dx.doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":12,"title":["The Natural Diyne-Furan Fatty Acid EV-086 Is an Inhibitor of Fungal Delta-9 Fatty Acid Desaturation with Efficacy in a Model of Skin Dermatophytosis"],"prefix":"10.1128","volume":"58","author":[{"given":"Philipp","family":"Knechtle","sequence":"first","affiliation":[{"name":"Evolva SA, Reinach, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Melanie","family":"Diefenbacher","sequence":"additional","affiliation":[{"name":"Evolva SA, Reinach, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katrine B. V.","family":"Greve","sequence":"additional","affiliation":[{"name":"Evolva SA, Reinach, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Federico","family":"Brianza","sequence":"additional","affiliation":[{"name":"Evolva SA, Reinach, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christophe","family":"Folly","sequence":"additional","affiliation":[{"name":"Evolva SA, Reinach, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Harald","family":"Heider","sequence":"additional","affiliation":[{"name":"Evolva SA, Reinach, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Museer A.","family":"Lone","sequence":"additional","affiliation":[{"name":"Department of Biology, Division of Biochemistry, University of Fribourg, Fribourg, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lisa","family":"Long","sequence":"additional","affiliation":[{"name":"Center for Medical Mycology, University Hospitals of Cleveland, Cleveland, Ohio, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jean-Philippe","family":"Meyer","sequence":"additional","affiliation":[{"name":"Evolva SA, Reinach, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Patrick","family":"Roussel","sequence":"additional","affiliation":[{"name":"Evolva SA, Reinach, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mahmoud A.","family":"Ghannoum","sequence":"additional","affiliation":[{"name":"Center for Medical Mycology, University Hospitals of Cleveland, Cleveland, Ohio, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roger","family":"Schneiter","sequence":"additional","affiliation":[{"name":"Department of Biology, Division of Biochemistry, University of Fribourg, Fribourg, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexandra S.","family":"Sorensen","sequence":"additional","affiliation":[{"name":"Evolva SA, Reinach, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","volume-title":"Clinical mycology","author":"Anaissie EJ","year":"2009","unstructured":"AnaissieEJMcGinnisMRPfallerMA. 2009. 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