{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T01:05:38Z","timestamp":1789088738781,"version":"build-2803163510"},"reference-count":25,"publisher":"American Society for Microbiology","issue":"10","license":[{"start":{"date-parts":[[2007,10,1]],"date-time":"2007-10-01T00:00:00Z","timestamp":1191196800000},"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":[[2007,10]]},"abstract":"ABSTRACT<\/jats:title>\n \n Fatty acid synthase in the yeast\n Cryptococcus neoformans<\/jats:italic>\n is composed of two subunits encoded by\n FAS1<\/jats:italic>\n and\n FAS2<\/jats:italic>\n genes. We inserted a copper-regulated promoter (P\n \n CTR4<\/jats:italic>\n -\n 2<\/jats:italic>\n <\/jats:sub>\n ) to regulate\n FAS1<\/jats:italic>\n and\n FAS2<\/jats:italic>\n expression in\n Cryptococcus neoformans<\/jats:italic>\n (strains P\n \n CTR4<\/jats:italic>\n -\n 2<\/jats:italic>\n <\/jats:sub>\n \/\n FAS1<\/jats:italic>\n and P\n \n CTR4<\/jats:italic>\n -\n 2<\/jats:italic>\n <\/jats:sub>\n \/\n FAS2<\/jats:italic>\n , respectively). Both mutants showed growth rates similar to those of the wild type in a low-copper medium in which\n FAS1<\/jats:italic>\n and\n FAS2<\/jats:italic>\n were expressed, but even in the presence of exogenous fatty acids, strains were suppressed in growth under high-copper conditions. The treatment of\n C. neoformans<\/jats:italic>\n with fluconazole was shown to have an increased inhibitory activity and even became fungicidal when either\n FAS1<\/jats:italic>\n or\n FAS2<\/jats:italic>\n expression was suppressed. Furthermore, a subinhibitory dose of fluconazole showed anticryptococcal activity in vitro in the presence of cerulenin, a fatty acid synthase inhibitor. In a murine model of pulmonary cryptococcosis, a tissue census of yeast cells in P\n \n CTR4<\/jats:italic>\n -\n 2<\/jats:italic>\n <\/jats:sub>\n \/\n FAS2<\/jats:italic>\n strain at day 7 of infection was significantly lower than that in mice treated with tetrathiomolybdate, a copper chelator (\n P<\/jats:italic>\n < 0.05), and a yeast census of P\n \n CTR4<\/jats:italic>\n -\n 2<\/jats:italic>\n <\/jats:sub>\n \/\n FAS1<\/jats:italic>\n strain at day 14 of infection in the brain was lower in the presence of more copper. In fact, no positive cultures from the brain were detected in mice (with or without tetrathiomolybdate treatment) infected with the P\n \n CTR4<\/jats:italic>\n -\n 2<\/jats:italic>\n <\/jats:sub>\n \/\n FAS2<\/jats:italic>\n strain, which implies that this mutant did not reach the brain in mice. We conclude that both\n FAS1<\/jats:italic>\n and\n FAS2<\/jats:italic>\n in\n C. neoformans<\/jats:italic>\n are essential for in vitro and in vivo growth in conditions with and without exogenous fatty acids and that\n FAS1<\/jats:italic>\n and\n FAS2<\/jats:italic>\n can potentially be fungicidal targets for\n C. neoformans<\/jats:italic>\n with a potential for synergistic behavior with azoles.\n <\/jats:p>","DOI":"10.1128\/aac.00442-07","type":"journal-article","created":{"date-parts":[[2007,8,14]],"date-time":"2007-08-14T00:41:45Z","timestamp":1187052105000},"page":"3537-3545","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":56,"title":["Fatty Acid Synthesis Is Essential for Survival of\n Cryptococcus neoformans<\/i>\n and a Potential Fungicidal Target"],"prefix":"10.1128","volume":"51","author":[{"given":"Methee","family":"Chayakulkeeree","sequence":"first","affiliation":[{"name":"Department of Medicine"},{"name":"Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas H.","family":"Rude","sequence":"additional","affiliation":[{"name":"Department of Medicine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dena L.","family":"Toffaletti","sequence":"additional","affiliation":[{"name":"Department of Medicine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John R.","family":"Perfect","sequence":"additional","affiliation":[{"name":"Department of Medicine"},{"name":"Molecular Genetics and Microbiology, Duke University Medical Center, Durham, North Carolina, 27710"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.idc.2006.07.001"},{"key":"e_1_3_2_3_2","unstructured":"Abstr. 6th Int. Conf. Cryptococcus Cryptococcosis 2005"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1097\/00005537-200104000-00024"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1099\/00221287-148-8-2607"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.04-0180"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M100884200"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)82077-4"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro1245"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1128\/EC.3.5.1249-1260.2004"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1021\/np020289t"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1128\/EC.4.2.487-489.2005"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)37757-3"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1002\/yea.1139"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.70.10.5684-5694.2002"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1432-1033.1992.tb16590.x"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1128\/MMBR.68.3.501-517.2004"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF00422073"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1567-1364.2006.00080.x"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1128\/EC.2.6.1336-1349.2003"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(19)84740-3"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1128\/jb.175.5.1405-1411.1993"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.nutr.21.1.97"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI30006"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1099\/00221287-142-9-2509"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.65.2.829-832.1997"}],"container-title":["Antimicrobial Agents and Chemotherapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/AAC.00442-07","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/AAC.00442-07","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,2,21]],"date-time":"2022-02-21T19:09:32Z","timestamp":1645470572000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/AAC.00442-07"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2007,10]]},"references-count":25,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2007,10]]}},"alternative-id":["10.1128\/AAC.00442-07"],"URL":"https:\/\/doi.org\/10.1128\/aac.00442-07","relation":{},"ISSN":["0066-4804","1098-6596"],"issn-type":[{"value":"0066-4804","type":"print"},{"value":"1098-6596","type":"electronic"}],"subject":[],"published":{"date-parts":[[2007,10]]},"assertion":[{"value":"2007-03-30","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2007-08-01","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2007-10-01","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}