{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T15:25:19Z","timestamp":1788535519835,"version":"build-2803163510"},"reference-count":49,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"25","content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Adv."],"published-print":{"date-parts":[[2025,6,20]]},"abstract":"<jats:p>\n            Intracellular parasites, including\n            <jats:italic toggle=\"yes\">Babesia<\/jats:italic>\n            and\n            <jats:italic toggle=\"yes\">Plasmodium<\/jats:italic>\n            , the agents of human babesiosis and malaria, depend on the salvage or de novo synthesis of critical nutrients for survival within human erythrocytes. Among these, polyamines play a pivotal role, but their specific requirements and molecular functions in intraerythrocytic parasites remain poorly understood. We identify spermidine as a key polyamine for\n            <jats:italic toggle=\"yes\">Babesia duncani<\/jats:italic>\n            and\n            <jats:italic toggle=\"yes\">Plasmodium falciparum<\/jats:italic>\n            for intraerythrocytic development. We demonstrate that spermidine is indispensable for regulating protein translation through hypusination of the eukaryotic translation initiation factor eIF5A, and its depletion leads to increased production of reactive oxygen species. Disruption of spermidine biosynthesis or its conversion from spermine results in parasite death. We also show that\n            <jats:italic toggle=\"yes\">B. duncani<\/jats:italic>\n            and other\n            <jats:italic toggle=\"yes\">Babesia<\/jats:italic>\n            species use an ancestral spermidine synthase\u2013like enzyme, highlighting a distinct evolutionary adaptation from\n            <jats:italic toggle=\"yes\">P. falciparum<\/jats:italic>\n            . Our results reveal the spermidine\u2019s dual role in oxidative stress defense and translation regulation, positioning spermidine biosynthesis as a critical vulnerability and a promising therapeutic target.\n          <\/jats:p>","DOI":"10.1126\/sciadv.adv2397","type":"journal-article","created":{"date-parts":[[2025,6,18]],"date-time":"2025-06-18T18:00:58Z","timestamp":1750269658000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":7,"title":["Spermidine is a key polyamine required by intracellular parasites for survival within host erythrocytes"],"prefix":"10.1126","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2318-5960","authenticated-orcid":true,"given":"Pallavi","family":"Singh","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, Section of Infectious Diseases, Yale School of Medicine, New Haven, CT, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9853-0987","authenticated-orcid":true,"given":"Jae-Yeon","family":"Choi","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Section of Infectious Diseases, Yale School of Medicine, New Haven, CT, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1202-1162","authenticated-orcid":true,"given":"Emmanuel","family":"Cornillot","sequence":"additional","affiliation":[{"name":"Institut de Biologie Computationnelle (IBC), and Institut de Recherche en Canc\u00e9rologie de Montpellier (IRCM - INSERM U1194), Institut r\u00e9gional du Cancer Montpellier (ICM) and Universit\u00e9 de Montpellier, Montpellier, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5028-1400","authenticated-orcid":true,"given":"Choukri Ben","family":"Mamoun","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Section of Infectious Diseases, Yale School of Medicine, New Haven, CT, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gks700"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0226781"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijpara.2018.11.007"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.3390\/diagnostics11060947"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.3390\/microorganisms9020440"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jiac181"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2017.01261"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2021.649184"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2018.05.018"},{"key":"e_1_3_2_11_2","first-page":"481","article-title":"Polyamines and their derivatives as modulators in growth and differentiation","volume":"62","author":"Canellakis Z. 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