{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T10:34:48Z","timestamp":1787567688726,"version":"build-2736575974"},"reference-count":80,"publisher":"eLife Sciences Publications, Ltd","license":[{"start":{"date-parts":[[2025,5,27]],"date-time":"2025-05-27T00:00:00Z","timestamp":1748304000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,5,27]],"date-time":"2025-05-27T00:00:00Z","timestamp":1748304000000},"content-version":"am","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,5,27]],"date-time":"2025-05-27T00:00:00Z","timestamp":1748304000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001501","name":"University Grants Commission India","doi-asserted-by":"publisher","award":["CSIR-UGC (2020\u20132021) fellowship"],"award-info":[{"award-number":["CSIR-UGC (2020\u20132021) fellowship"]}],"id":[{"id":"10.13039\/501100001501","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Prime Minister's Research Fellowship","award":["2021\u20132024"],"award-info":[{"award-number":["2021\u20132024"]}]},{"DOI":"10.13039\/501100001412","name":"Council of Scientific and Industrial Research","doi-asserted-by":"publisher","award":["GATE fellowship"],"award-info":[{"award-number":["GATE fellowship"]}],"id":[{"id":"10.13039\/501100001412","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001412","name":"Council of Scientific and Industrial Research","doi-asserted-by":"publisher","award":["CSIR fellowship"],"award-info":[{"award-number":["CSIR fellowship"]}],"id":[{"id":"10.13039\/501100001412","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elifesciences.org"],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:p>\n                    The management of\n                    <jats:italic>Leishmania donovani<\/jats:italic>\n                    (LD), responsible for fatal visceral leishmaniasis (VL), faces increasing challenges due to rising drug unresponsiveness, leading to increasing treatment failures. While hypolipidemia characterizes VL, LD, a cholesterol auxotroph, relies on host lipid scavenging for its intracellular survival. The aggressive pathology, in terms of increased organ parasite load, observed in hosts infected with antimony-unresponsive-LD (LD-R) as compared to their sensitive counterparts (LD-S), highlights LD-R\u2019s heightened reliance on host lipids. Here, we report that LD-R-infection in mice promotes fluid-phase endocytosis in the host macrophages, selectively accumulating neutral lipids while excluding oxidized-low-density lipoprotein (LDL). LD-R enhances the fusion of endocytosed LDL-vesicles with its phagolysosomal membrane and inhibits cholesterol mobilization from these vesicles by suppressing NPC-1. This provides LD-R amastigotes with excess lipids, supporting their rapid proliferation and membrane synthesis. This excess LDL-influx leads to an eventual accumulation of neutral lipid droplets around LD-R amastigotes, thereby increasing their unresponsiveness toward Amphotericin-B, a second-line amphiphilic antileishmanial. Notably, VL patients showing relapse with Amphotericin-B treatment exhibited significantly lower serum LDL and cholesterol than cured cases. Treatment with Aspirin, a lipid droplet blocker, reduced lipid droplets around LD-R amastigotes, restoring Amphotericin-B responsiveness.\n                  <\/jats:p>","DOI":"10.7554\/elife.102857","type":"journal-article","created":{"date-parts":[[2025,2,7]],"date-time":"2025-02-07T03:28:19Z","timestamp":1738898899000},"update-policy":"https:\/\/doi.org\/10.7554\/elife.102857","source":"Crossref","is-referenced-by-count":5,"title":["Scrutinized lipid utilization disrupts Amphotericin-B responsiveness in clinical isolates of Leishmania donovani"],"prefix":"10.7554","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-6573-8196","authenticated-orcid":true,"given":"Supratim","family":"Pradhan","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03w5sq511","id-type":"ROR","asserted-by":"publisher"}],"name":"School of Medical Science and Technology, Indian Institute of Technology Kharagpur","place":["Kharagpur, 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