{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T01:29:29Z","timestamp":1787016569332,"version":"build-2736575974"},"reference-count":41,"publisher":"American Society for Microbiology","issue":"2","license":[{"start":{"date-parts":[[2006,2,1]],"date-time":"2006-02-01T00:00:00Z","timestamp":1138752000000},"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":[[2006,2]]},"abstract":"ABSTRACT<\/jats:title>\n \n The alkyl phosphocholine drug miltefosine is structurally similar to natural substrates of the fungal virulence determinant phospholipase B1 (PLB1), which is a potential drug target. We determined the MICs of miltefosine against key fungal pathogens, correlated antifungal activity with inhibition of the PLB1 activities (PLB, lysophospholipase [LPL], and lysophospholipase-transacylase [LPTA]), and investigated its efficacy in a mouse model of disseminated cryptococcosis. Miltefosine inhibited secreted cryptococcal LPTA activity by 35% at the subhemolytic concentration of 25 \u03bcM (10.2 \u03bcg\/ml) and was inactive against mammalian pancreatic phospholipase A2 (PLA\n 2<\/jats:sub>\n ). At 250 \u03bcM, cytosolic PLB, LPL, and LPTA activities were inhibited by 25%, 51%, and 77%, respectively. The MICs at which 90% of isolates were inhibited (MIC\n 90<\/jats:sub>\n s) against\n Candida albicans<\/jats:italic>\n ,\n Candida glabrata<\/jats:italic>\n ,\n Candida krusei<\/jats:italic>\n ,\n Cryptococcus neoformans<\/jats:italic>\n ,\n Cryptococcus gattii<\/jats:italic>\n ,\n Aspergillus fumigatus<\/jats:italic>\n ,\n Fusarium solani<\/jats:italic>\n ,\n Scedosporium prolificans<\/jats:italic>\n , and\n Scedosporium apiospermum<\/jats:italic>\n were 2 to 4 \u03bcg\/ml. The MICs of miltefosine against\n Candida tropicalis<\/jats:italic>\n (\n n<\/jats:italic>\n = 8) were 2 to 4 \u03bcg\/ml, those against\n Aspergillus terreus<\/jats:italic>\n and\n Candida parapsilosis<\/jats:italic>\n were 8 \u03bcg\/ml (MIC\n 90<\/jats:sub>\n ), and those against\n Aspergillus flavus<\/jats:italic>\n (\n n<\/jats:italic>\n = 8) were 2 to 16 \u03bcg\/ml. Miltefosine was fungicidal for\n C. neoformans<\/jats:italic>\n , with rates of killing of 2 log units within 4 h at 7.0 \u03bcM (2.8 \u03bcg\/ml). Miltefosine given orally to mice on days 1 to 5 after intravenous infection with\n C. neoformans<\/jats:italic>\n delayed the development of illness and mortality and significantly reduced the brain cryptococcal burden. We conclude that miltefosine has broad-spectrum antifungal activity and is active in vivo in a mouse model of disseminated cryptococcosis. The relatively small inhibitory effect on PLB1 enzyme activities at concentrations exceeding the MIC by 2 to 20 times suggests that PLB1 inhibition is not the only mechanism of the antifungal effect.\n <\/jats:p>","DOI":"10.1128\/aac.50.2.414-421.2006","type":"journal-article","created":{"date-parts":[[2006,1,25]],"date-time":"2006-01-25T16:53:41Z","timestamp":1138208021000},"page":"414-421","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":132,"title":["Hexadecylphosphocholine (Miltefosine) Has Broad-Spectrum Fungicidal Activity and Is Efficacious in a Mouse Model of Cryptococcosis"],"prefix":"10.1128","volume":"50","author":[{"given":"Fred","family":"Widmer","sequence":"first","affiliation":[{"name":"Centre for Infectious Diseases and Microbiology, University of Sydney at Westmead, and Department of Infectious Diseases, ICPMR Building, Westmead Hospital, Westmead, NSW 2145"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lesley C.","family":"Wright","sequence":"additional","affiliation":[{"name":"Centre for Infectious Diseases and Microbiology, University of Sydney at Westmead, and Department of Infectious Diseases, ICPMR Building, Westmead Hospital, Westmead, NSW 2145"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Obando","sequence":"additional","affiliation":[{"name":"Centre for Infectious Diseases and Microbiology, University of Sydney at Westmead, and Department of Infectious Diseases, ICPMR Building, Westmead Hospital, Westmead, NSW 2145"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosemary","family":"Handke","sequence":"additional","affiliation":[{"name":"Women's and Children's Hospital, North Adelaide, South Australia 5006, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ranjini","family":"Ganendren","sequence":"additional","affiliation":[{"name":"Centre for Infectious Diseases and Microbiology, University of Sydney at Westmead, and Department of Infectious Diseases, ICPMR Building, Westmead Hospital, Westmead, NSW 2145"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David H.","family":"Ellis","sequence":"additional","affiliation":[{"name":"Women's and Children's Hospital, North Adelaide, South Australia 5006, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tania C.","family":"Sorrell","sequence":"additional","affiliation":[{"name":"Centre for Infectious Diseases and Microbiology, University of Sydney at Westmead, and Department of Infectious Diseases, ICPMR Building, Westmead Hospital, Westmead, NSW 2145"},{"name":"Centre for Clinical Research Excellence in Infections & Bioethics in Haematological Malignancies, University of Sydney, Sydney, NSW 2006"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.chemphyslip.2003.08.002"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.64.3.751-755.1996"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1139\/o59-099"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF02535556"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.65.2.405-411.1997"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/175.2.414"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1042\/bj3470431"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2958.2001.02236.x"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0166-6851(02)00283-9"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.2174\/1389557043487439"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1042\/bst0170274"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.48.5.1561-1569.2004"},{"key":"e_1_3_2_14_2","unstructured":"Microbes Infect."},{"key":"e_1_3_2_15_2","first-page":"1091","volume":"14","year":"1986","unstructured":"Gautam, C. 1986. 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