{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T01:12:48Z","timestamp":1791162768535,"version":"4.1.0"},"reference-count":35,"publisher":"American Society for Microbiology","issue":"8","license":[{"start":{"date-parts":[[2003,8,1]],"date-time":"2003-08-01T00:00:00Z","timestamp":1059696000000},"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":[[2003,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Miltefosine (hexadecylphosphocholine [HePC]) is the first drug approved for the oral treatment of visceral leishmaniasis. As part of a study on the mechanisms of action of this drug and on the rates of resistance to this drug, we have been working in vitro with an\n            <jats:italic>Leishmania donovani<\/jats:italic>\n            line that was previously shown to be 15-fold more resistant to HePC. We have studied the accumulation of [\n            <jats:sup>14<\/jats:sup>\n            C]HePC by\n            <jats:italic>L. donovani<\/jats:italic>\n            promastigotes and have found a drastic reduction (&gt;95%) in the ability of the resistant line to internalize the drug. Binding of HePC to the plasma membrane and drug efflux from preloaded cells were similar in both drug-sensitive and -resistant lines, and no [\n            <jats:sup>14<\/jats:sup>\n            C]HePC metabolism was evident in either line. Resistant parasites were also unable to take up other short-chain phospholipid analogs, independently of their polar head group, even though endocytosis remained unaltered. Finally, HePC uptake was temperature and energy dependent and sensitive to the thiol-reactive agent\n            <jats:italic>N<\/jats:italic>\n            -ethylmaleimide. We propose that inward translocation of a short-chain phospholipid across the plasma membrane may exist in\n            <jats:italic>Leishmania<\/jats:italic>\n            promastigotes and that such activity is defective in the resistant line.\n          <\/jats:p>","DOI":"10.1128\/aac.47.8.2397-2403.2003","type":"journal-article","created":{"date-parts":[[2003,7,23]],"date-time":"2003-07-23T19:24:32Z","timestamp":1058988272000},"page":"2397-2403","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":150,"title":["<i>Leishmania donovani<\/i>\n            Resistance to Miltefosine Involves a Defective Inward Translocation of the Drug"],"prefix":"10.1128","volume":"47","author":[{"given":"F. Javier","family":"Pe\u0301rez-Victoria","sequence":"first","affiliation":[{"name":"Instituto de Parasitologi\u0301a y Biomedicina \u201cLo\u0301pez-Neyra,\u201d Consejo Superior de Investigaciones Cienti\u0301ficas, Granada, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Santiago","family":"Castanys","sequence":"additional","affiliation":[{"name":"Instituto de Parasitologi\u0301a y Biomedicina \u201cLo\u0301pez-Neyra,\u201d Consejo Superior de Investigaciones Cienti\u0301ficas, Granada, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francisco","family":"Gamarro","sequence":"additional","affiliation":[{"name":"Instituto de Parasitologi\u0301a y Biomedicina \u201cLo\u0301pez-Neyra,\u201d Consejo Superior de Investigaciones Cienti\u0301ficas, Granada, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1016\/0166-6851(87)90080-6","volume":"26","year":"1987","unstructured":"Achterberg, V., and G. 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