{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T21:10:12Z","timestamp":1791234612073,"version":"4.1.0"},"reference-count":32,"publisher":"American Society for Microbiology","issue":"7","license":[{"start":{"date-parts":[[2005,7,1]],"date-time":"2005-07-01T00:00:00Z","timestamp":1120176000000},"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":[[2005,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Miltefosine (hexadecylphosphocholine [HePC]) is the first orally active drug approved for the treatment of visceral leishmaniasis. In order to investigate the biochemical modifications occurring in HePC-resistant (HePC-R)\n            <jats:italic>Leishmania donovani<\/jats:italic>\n            promastigotes, taking into account the lipid nature of HePC, we investigated their fatty acid and sterol metabolisms. We found that the content of unsaturated phospholipid alkyl chains was lower in HePC-R parasite plasma membranes than in those of the wild type, suggesting a lower fluidity of HePC-R parasite membranes. We also demonstrated that HePC insertion within an external monolayer was more difficult when the proportion of unsaturated phospholipids decreased, rendering the HePC interaction with the external monolayer of HePC-R parasites more difficult. Furthermore, HePC-R parasite membranes displayed a higher content of short alkyl chain fatty acids, suggesting a partial inactivation of the fatty acid elongation enzyme system in HePC-R parasites. Sterol biosynthesis was found to be modified in HePC-R parasites, since the 24-alkylated sterol content was halved in HePC-R parasites; however, this modification was not related to HePC sensitivity. In conclusion, HePC resistance affects three lipid biochemical pathways: fatty acid elongation, the desaturase system responsible for fatty acid alkyl chain unsaturation, and the C-24-alkylation of sterols.\n          <\/jats:p>","DOI":"10.1128\/aac.49.7.2677-2686.2005","type":"journal-article","created":{"date-parts":[[2005,6,25]],"date-time":"2005-06-25T02:22:50Z","timestamp":1119666170000},"page":"2677-2686","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":121,"title":["Alteration of Fatty Acid and Sterol Metabolism in Miltefosine-Resistant\n            <i>Leishmania donovani<\/i>\n            Promastigotes and Consequences for Drug-Membrane Interactions"],"prefix":"10.1128","volume":"49","author":[{"given":"M.","family":"Rakotomanga","sequence":"first","affiliation":[{"name":"Chimiothe\u0301rapie Antiparasitaire, UMR 8076 CNRS, Faculte\u0301 de Pharmacie, Universite\u0301 Paris XI, F-92290 Cha\u0304tenay-Malabry, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Saint-Pierre-Chazalet","sequence":"additional","affiliation":[{"name":"Chimiothe\u0301rapie Antiparasitaire, UMR 8076 CNRS, Faculte\u0301 de Pharmacie, Universite\u0301 Paris XI, F-92290 Cha\u0304tenay-Malabry, France"},{"name":"Laboratoire de Physicochimie Biomole\u0301culaire et Cellulaire, UMR 7033 CNRS, Universite\u0301 Pierre et Marie Curie-Paris VI, 75252 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P. 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