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In the present study, transcriptional profiling coupled with mutant and biochemical analyses were conducted using the model yeast<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Saccharomyces cerevisiae<\/jats:named-content>to investigate its mechanism of action. 6-NDA elicited a transcriptome response indicative of fatty acid stress, altering the expression of genes that are required for yeast growth in the presence of oleate. Mutants of<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">S. cerevisiae<\/jats:named-content>lacking transcription factors that regulate fatty acid \u03b2-oxidation showed increased sensitivity to 6-NDA. Fatty acid profile analysis indicated that 6-NDA inhibited the formation of fatty acids longer than 14 carbons in length. In addition, the growth inhibitory effect of 6-NDA was rescued in the presence of exogenously supplied oleate. To investigate the response of a pathogenic fungal species to 6-NDA, transcriptional profiling and biochemical analyses were also conducted in<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">C. albicans<\/jats:named-content>. The transcriptional response and fatty acid profile of<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">C. albicans<\/jats:named-content>were comparable to those obtained in<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">S. cerevisiae<\/jats:named-content>, and the rescue of growth inhibition with exogenous oleate was also observed in<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">C. albicans<\/jats:named-content>. In a fluconazole-resistant clinical isolate of<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">C. albicans<\/jats:named-content>, a fungicidal effect was produced when fluconazole was combined with 6-NDA. In hyphal growth assays, 6-NDA inhibited the formation of long hyphal filaments in<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">C. albicans<\/jats:named-content>. Collectively, our results indicate that the antifungal activity of 6-NDA is mediated by a disruption in fatty acid homeostasis and that 6-NDA has potential utility in the treatment of superficial<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Candida<\/jats:named-content>infections.<\/jats:p>","DOI":"10.1128\/aac.05663-11","type":"journal-article","created":{"date-parts":[[2012,3,20]],"date-time":"2012-03-20T03:32:13Z","timestamp":1332214333000},"page":"2894-2907","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":26,"title":["A Potent Plant-Derived Antifungal Acetylenic Acid Mediates Its Activity by Interfering with Fatty Acid Homeostasis"],"prefix":"10.1128","volume":"56","author":[{"given":"Tao","family":"Xu","sequence":"first","affiliation":[{"name":"National Center for Natural Products Research, University of Mississippi, University, Mississippi, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siddharth K.","family":"Tripathi","sequence":"additional","affiliation":[{"name":"National Center for Natural Products Research, University of Mississippi, University, Mississippi, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qin","family":"Feng","sequence":"additional","affiliation":[{"name":"National Center for Natural Products Research, University of Mississippi, University, Mississippi, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael C.","family":"Lorenz","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Molecular Genetics, The University of Texas Health Science Center at Houston, Houston, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marsha A.","family":"Wright","sequence":"additional","affiliation":[{"name":"National Center for Natural Products Research, University of Mississippi, University, Mississippi, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melissa R.","family":"Jacob","sequence":"additional","affiliation":[{"name":"National Center for Natural Products Research, University of Mississippi, University, Mississippi, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melanie M.","family":"Mask","sequence":"additional","affiliation":[{"name":"Natural Products Utilization Research Unit, Agricultural Research Service, United States Department of Agriculture, University, Mississippi, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott R.","family":"Baerson","sequence":"additional","affiliation":[{"name":"Natural Products Utilization Research Unit, Agricultural Research Service, United States Department of Agriculture, University, Mississippi, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xing-Cong","family":"Li","sequence":"additional","affiliation":[{"name":"National Center for Natural Products Research, University of Mississippi, University, Mississippi, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alice M.","family":"Clark","sequence":"additional","affiliation":[{"name":"National Center for Natural Products Research, University of Mississippi, University, Mississippi, USA"},{"name":"Department of Pharmacognosy, University of Mississippi, University, Mississippi, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ameeta K.","family":"Agarwal","sequence":"additional","affiliation":[{"name":"National Center for Natural Products Research, University of Mississippi, University, Mississippi, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1128\/EC.00323-07"},{"key":"e_1_3_3_3_2","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1021\/tx00020a011","article-title":"9-Octadecynoic acid: a novel DNA binding agent","volume":"4","author":"Berry DE","year":"1991","unstructured":"BerryDE ChanJA MacKenzieL HechtSM. 1991. 9-Octadecynoic acid: a novel DNA binding agent. 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