{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T08:18:50Z","timestamp":1789805930571,"version":"4.0.1"},"reference-count":23,"publisher":"American Society for Microbiology","issue":"4","license":[{"start":{"date-parts":[[2009,4,1]],"date-time":"2009-04-01T00:00:00Z","timestamp":1238544000000},"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":[[2009,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Miltefosine (hexadecylphosphocholine, MLF) is the first oral drug with recognized efficacy against both visceral and cutaneous leishmaniasis. However, some clinical studies have suggested that MLF shows significantly less efficiency against the cutaneous leishmaniasis caused by\n            <jats:italic>Leishmania braziliensis<\/jats:italic>\n            . In this work, we have determined the cellular and molecular basis for the natural MLF resistance observed in\n            <jats:italic>L<\/jats:italic>\n            .\n            <jats:italic>braziliensis<\/jats:italic>\n            . Four independent\n            <jats:italic>L<\/jats:italic>\n            .\n            <jats:italic>braziliensis<\/jats:italic>\n            clinical isolates showed a marked decrease in MLF sensitivity that was due to their inability to internalize the drug. MLF internalization in the highly sensitive\n            <jats:italic>L<\/jats:italic>\n            .\n            <jats:italic>donovani<\/jats:italic>\n            species requires at least two proteins in the plasma membrane, LdMT, a P-type ATPase involved in phospholipid translocation, and its \u03b2 subunit, LdRos3. Strikingly,\n            <jats:italic>L<\/jats:italic>\n            .\n            <jats:italic>braziliensis<\/jats:italic>\n            parasites showed highly reduced levels of this MLF translocation machinery at the plasma membrane, mainly because of the low expression levels of the \u03b2 subunit, LbRos3. Overexpression of LbRos3 induces increased MLF sensitivity not only in\n            <jats:italic>L<\/jats:italic>\n            .\n            <jats:italic>braziliensis<\/jats:italic>\n            promastigotes but also in intracellular amastigotes. These results further highlight the importance of the MLF translocation machinery in determining MLF potency and point toward the development of protocols to routinely monitor MLF susceptibility in geographic areas where\n            <jats:italic>L<\/jats:italic>\n            .\n            <jats:italic>braziliensis<\/jats:italic>\n            might be prevalent.\n          <\/jats:p>","DOI":"10.1128\/aac.01694-08","type":"journal-article","created":{"date-parts":[[2009,2,3]],"date-time":"2009-02-03T01:54:59Z","timestamp":1233626099000},"page":"1305-1313","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":71,"title":["Low Plasma Membrane Expression of the Miltefosine Transport Complex Renders\n            <i>Leishmania braziliensis<\/i>\n            Refractory to the Drug"],"prefix":"10.1128","volume":"53","author":[{"given":"Mari\u0301a P.","family":"Sa\u0301nchez-Can\u0303ete","sequence":"first","affiliation":[{"name":"Instituto de Parasitologi\u0301a y Biomedicina Lo\u0301pez-Neyra, CSIC, Parque Tecnolo\u0301gico de Ciencias de la Salud, Avda. del Conocimiento s\/n, 18100 Armilla, Granada, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lui\u0301s","family":"Carvalho","sequence":"additional","affiliation":[{"name":"Instituto de Parasitologi\u0301a y Biomedicina Lo\u0301pez-Neyra, CSIC, Parque Tecnolo\u0301gico de Ciencias de la Salud, Avda. del Conocimiento s\/n, 18100 Armilla, Granada, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F. Javier","family":"Pe\u0301rez-Victoria","sequence":"additional","affiliation":[{"name":"Instituto de Parasitologi\u0301a y Biomedicina Lo\u0301pez-Neyra, CSIC, Parque Tecnolo\u0301gico de Ciencias de la Salud, Avda. del Conocimiento s\/n, 18100 Armilla, Granada, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francisco","family":"Gamarro","sequence":"additional","affiliation":[{"name":"Instituto de Parasitologi\u0301a y Biomedicina Lo\u0301pez-Neyra, CSIC, Parque Tecnolo\u0301gico de Ciencias de la Salud, Avda. del Conocimiento s\/n, 18100 Armilla, Granada, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Santiago","family":"Castanys","sequence":"additional","affiliation":[{"name":"Instituto de Parasitologi\u0301a y Biomedicina Lo\u0301pez-Neyra, CSIC, Parque Tecnolo\u0301gico de Ciencias de la Salud, Avda. del Conocimiento s\/n, 18100 Armilla, Granada, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"crossref","first-page":"250","DOI":"10.1016\/S0006-291X(03)00947-1","volume":"306","year":"2003","unstructured":"Ara\u00fajo-Santos, J. 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