{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T03:46:19Z","timestamp":1790739979914,"version":"4.1.0"},"reference-count":62,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,3,12]],"date-time":"2021-03-12T00:00:00Z","timestamp":1615507200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Infect. Microbiol."],"abstract":"<jats:p>Erythrocytes possess an unusual programmed cell death mechanism termed eryptosis, and several compounds have been previously claimed to induce eryptosis <jats:italic>in vitro<\/jats:italic>. Malaria parasites (genus <jats:italic>Plasmodium<\/jats:italic>) reside in erythrocytes during the pathogenic part of their life cycle, and the potential of several eryptosis inducers to act as antimalarials has been tested in recent years. However, the eryptosis-inducing capacity of these compounds varies significantly between eryptosis-focused studies and malaria investigations. Here, we investigated the reasons for these discrepancies, we developed a protocol to investigate eryptosis in malaria cultures and we re-evaluated the potential of eryptosis inducers as antimalarials. First, we showed that eryptosis read-out <jats:italic>in vitro<\/jats:italic> is dependent on culture conditions. Indeed, conditions that have consistently been used to study eryptosis do not support <jats:italic>P. falciparum<\/jats:italic> growth and prime erythrocytes for eryptosis. Next, we defined culture conditions that allow the detection of eryptosis while supporting <jats:italic>P. falciparum<\/jats:italic> survival. Finally, we selected six eryptosis-inducers based on their clinical use, molecular target and antimalarial activities, and re-evaluated their eryptosis inducing capacities and their potential as antimalarials. We demonstrate that none of these compounds affect the viability of na\u00efve or <jats:italic>P. falciparum<\/jats:italic>-infected erythrocytes <jats:italic>in vitro<\/jats:italic>. Nevertheless, three of these compounds impair parasite development, although through a mechanism unrelated to eryptosis and yet to be elucidated. We conclude that careful consideration of experimental set up is key for the accurate assessment of the eryptosis-inducing potential of compounds and their evaluation as potential antimalarials.<\/jats:p>","DOI":"10.3389\/fcimb.2021.630812","type":"journal-article","created":{"date-parts":[[2021,3,12]],"date-time":"2021-03-12T06:42:38Z","timestamp":1615531358000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":17,"title":["Eryptosis and Malaria: New Experimental Guidelines and Re-Evaluation of the Antimalarial Potential of Eryptosis Inducers"],"prefix":"10.3389","volume":"11","author":[{"given":"Coralie","family":"Boulet","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taylah L.","family":"Gaynor","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teresa G.","family":"Carvalho","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,3,12]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1186\/1475-2875-9-118","article-title":"Beneficial effect of aurothiomalate on murine malaria","volume":"9","author":"Alesutan","year":"2010","journal-title":"Malar J."},{"key":"B2","doi-asserted-by":"publisher","first-page":"1795","DOI":"10.1002\/ptr.6113","article-title":"Apigenin inhibits growth of the Plasmodium berghei and disrupts some metabolic pathways in mice","volume":"32","author":"Amiri","year":"2018","journal-title":"Phytother Res."},{"key":"B3","doi-asserted-by":"publisher","first-page":"716","DOI":"10.1128\/AAC.01144-06","article-title":"High-Throughput Plasmodium falciparum Growth Assay for Malaria Drug Discovery","volume":"51","author":"Baniecki","year":"2007","journal-title":"Antimicrobial Agents Chemother"},{"key":"B4","doi-asserted-by":"publisher","first-page":"1435","DOI":"10.1093\/infdis\/jiz334","article-title":"Antiphosphatidylserine Immunoglobulin M and Immunoglobulin G Antibodies Are Higher in Vivax Than Falciparum Malaria, and Associated With Early Anemia in Both Species","volume":"220","author":"Barber","year":"2019","journal-title":"J. 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