{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T12:22:27Z","timestamp":1788438147274,"version":"build-2803163510"},"reference-count":72,"publisher":"Public Library of Science (PLoS)","issue":"1","license":[{"start":{"date-parts":[[2025,1,31]],"date-time":"2025-01-31T00:00:00Z","timestamp":1738281600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001411","name":"Indian Council of Medical Research","doi-asserted-by":"publisher","award":["6\/9-7(297)\/2022-ECD-II"],"award-info":[{"award-number":["6\/9-7(297)\/2022-ECD-II"]}],"id":[{"id":"10.13039\/501100001411","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Scheme for Transformational and Advanced Research in Sciences","award":["MoE-STARS\/STARS-2\/2023-0516"],"award-info":[{"award-number":["MoE-STARS\/STARS-2\/2023-0516"]}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>Despite the withdrawal of pentavalent-antimonials in treating Visceral leishmaniasis from India, recent clinical isolates of <jats:italic>Leishmania donovani<\/jats:italic> (LD) exhibit unresponsiveness towards pentavalent-antimony (LD-R). This antimony-unresponsiveness points towards a genetic adaptation that underpins LD-R\u2019s evolutionary persistence and dominance over sensitive counterparts (LD-S). This study highlights how LD evolutionarily tackled antimony exposure and gained increased potential of scavenging host-iron within its parasitophorous vacuoles (PV) to support its aggressive proliferation. Even though anti-leishmanial activity of pentavalent antimonials relies on triggering oxidative outburst, LD-R exhibits a surprising strategy of promoting reactive oxygen species (ROS) generation in infected macrophages. An inherent metabolic shift from glycolysis to Pentose Phosphate shunt allows LD-R to withstand elevated ROS by sustaining heightened levels of NADPH. Elevated ROS levels on the other hand trigger excess iron production, and LD-R capitalizes on this surplus iron by selectively reshuffling macrophage-surface iron exporter, Ferroportin, around its PV thereby gaining a survival edge as a heme-auxotroph. Higher iron utilization by LD-R leads to subsequent iron insufficiency, compensated by increased erythrophagocytosis through the breakdown of SIRP\u03b1-CD47 surveillance, orchestrated by a complex interplay of two proteases, Furin and ADAM10. Understanding these mechanisms is crucial for managing LD-R-infections and their associated complications like severe anemia, and may also provide valuable mechanistic insights into understanding drug unresponsiveness developed in other intracellular pathogens that rely on host iron.<\/jats:p>","DOI":"10.1371\/journal.ppat.1012858","type":"journal-article","created":{"date-parts":[[2025,1,31]],"date-time":"2025-01-31T18:51:00Z","timestamp":1738349460000},"page":"e1012858","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":2,"title":["Oxidative stress-driven enhanced iron production and scavenging through Ferroportin reorientation worsens anemia in antimony-resistant Leishmania donovani infection"],"prefix":"10.1371","volume":"21","author":[{"given":"Souradeepa","family":"Ghosh","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Krishna 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