{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T19:30:31Z","timestamp":1768505431749,"version":"3.49.0"},"posted":{"date-parts":[[2023,5,16]]},"group-title":"Microbiology","reference-count":48,"publisher":"openRxiv","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2023,5,16]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Malaria is a highly oxidative parasitic disease in which anemia is the most common clinical symptom. A major contributor to malarial anemia pathogenesis is the destruction of bystander, uninfected red blood cells. Metabolic fluctuations are known to occur in the plasma of individuals with acute malaria, emphasizing the role of metabolic changes in disease progression and severity. Here, we report that conditioned media from\n                  <jats:italic>Plasmodium falciparum<\/jats:italic>\n                  culture induces oxidative stress in healthy uninfected RBCs. Additionally, we show the benefit of amino acid pre-exposure for RBCs and how this pre-treatment intrinsically prepares RBCs to mitigate oxidative stress.\n                <\/jats:p>\n                <jats:sec>\n                  <jats:title>Key points<\/jats:title>\n                  <jats:list list-type=\"bullet\">\n                    <jats:list-item>\n                      <jats:p>\n                        Intracellular ROS is acquired in red blood cells incubated with\n                        <jats:italic>Plasmodium falciparum<\/jats:italic>\n                        conditioned media\n                      <\/jats:p>\n                    <\/jats:list-item>\n                    <jats:list-item>\n                      <jats:p>Glutamine, cysteine, and glycine amino acid supplementation increased glutathione biosynthesis and reduced ROS levels in stressed RBCs<\/jats:p>\n                    <\/jats:list-item>\n                  <\/jats:list>\n                <\/jats:sec>","DOI":"10.1101\/2023.05.16.540951","type":"posted-content","created":{"date-parts":[[2023,5,17]],"date-time":"2023-05-17T00:40:12Z","timestamp":1684284012000},"source":"Crossref","is-referenced-by-count":0,"title":["Amino acid supplementation confers protection to red blood cells prior to Plasmodium falciparum bystander stress"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4979-879X","authenticated-orcid":false,"given":"Heather Colvin","family":"Binns","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elmira","family":"Alipour","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dinah S.","family":"Nahid","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John F.","family":"Whitesides","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anderson O\u2019Brien","family":"Cox","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cristina M.","family":"Furdui","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Glen S.","family":"Marrs","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel B.","family":"Kim-Shapiro","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5369-0215","authenticated-orcid":false,"given":"Regina Joice","family":"Cordy","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"key":"2023051820401209000_2023.05.16.540951v1.1","unstructured":"Global Malaria Programme. World malaria report 2022."},{"key":"2023051820401209000_2023.05.16.540951v1.2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2006-09-018069"},{"key":"2023051820401209000_2023.05.16.540951v1.3","doi-asserted-by":"publisher","DOI":"10.1017\/S0031182099004564"},{"key":"2023051820401209000_2023.05.16.540951v1.4","doi-asserted-by":"publisher","DOI":"10.1016\/S0035-9203(02)90100-8"},{"key":"2023051820401209000_2023.05.16.540951v1.5","doi-asserted-by":"crossref","unstructured":"Barber BE , Russell B , Grigg MJ , et al. Reduced red blood cell deformability in Plasmodium knowlesi malaria. 2018;","DOI":"10.1182\/bloodadvances.2017013730"},{"key":"2023051820401209000_2023.05.16.540951v1.6","doi-asserted-by":"publisher","DOI":"10.1007\/s00430-014-0347-0"},{"key":"2023051820401209000_2023.05.16.540951v1.7","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2016.01.009"},{"issue":"12","key":"2023051820401209000_2023.05.16.540951v1.8","doi-asserted-by":"crossref","first-page":"1381","DOI":"10.1182\/blood.2019004746","article-title":"Plasmodium falciparum sexual parasites develop in human erythroblasts and affect erythropoiesis","volume":"136","year":"2020","journal-title":"Blood"},{"key":"2023051820401209000_2023.05.16.540951v1.9","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.abj1008"},{"key":"2023051820401209000_2023.05.16.540951v1.10","doi-asserted-by":"crossref","unstructured":"Jezewski AJ , Lin Y-H , Reisz JA , et al. Targeting Host Glycolysis as a Strategy for Antimalarial Development. Front. Cell. Infect. Microbiol. 2021;11:730413.","DOI":"10.3389\/fcimb.2021.730413"},{"issue":"4","key":"2023051820401209000_2023.05.16.540951v1.11","first-page":"353","article-title":"Red blood cell metabolism in experimental animals: pentose phosphate pathway, antioxidant enzymes and glutathione","volume":"34","year":"1985","journal-title":"Jikken Dobutsu"},{"key":"2023051820401209000_2023.05.16.540951v1.12","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2008.2081"},{"issue":"12","key":"2023051820401209000_2023.05.16.540951v1.13","doi-asserted-by":"crossref","first-page":"16346","DOI":"10.3390\/ijms131216346","article-title":"Oxidative Stress in Malaria","volume":"13","year":"2012","journal-title":"IJMS"},{"issue":"2","key":"2023051820401209000_2023.05.16.540951v1.14","doi-asserted-by":"crossref","first-page":"17","DOI":"10.3390\/medsci7020017","article-title":"Oxidative Profile of Patients with Sickle Cell Disease","volume":"7","year":"2019","journal-title":"Medical Sciences"},{"issue":"3","key":"2023051820401209000_2023.05.16.540951v1.15","first-page":"127","article-title":"Superoxide dismutase and catalase activities in red cells of patients with Plasmodium falciparum","volume":"70","year":"1987","journal-title":"J Med Assoc Thai"},{"key":"2023051820401209000_2023.05.16.540951v1.16","doi-asserted-by":"crossref","unstructured":"Cordy RJ , Patrapuvich R , Lili LN , et al. Distinct amino acid and lipid perturbations characterize acute versus chronic malaria. JCI Insight. 2019;4(9):.","DOI":"10.1172\/jci.insight.125156"},{"issue":"1","key":"2023051820401209000_2023.05.16.540951v1.17","doi-asserted-by":"crossref","first-page":"2875","DOI":"10.1038\/s41598-018-37816-9","article-title":"Insights into physiological roles of unique metabolites released from Plasmodium-infected RBCs and their potential as clinical biomarkers for malaria","volume":"9","year":"2019","journal-title":"Scientific Reports"},{"key":"2023051820401209000_2023.05.16.540951v1.18","doi-asserted-by":"crossref","unstructured":"Leopold SJ , Apinan S , Ghose A , et al. Amino acid derangements in adults with severe falciparum malaria. Scientific Reports. 2019;9(1):.","DOI":"10.1038\/s41598-019-43044-6"},{"key":"2023051820401209000_2023.05.16.540951v1.19","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jiy727"},{"issue":"9358","key":"2023051820401209000_2023.05.16.540951v1.20","doi-asserted-by":"crossref","first-page":"676","DOI":"10.1016\/S0140-6736(03)12564-0","article-title":"Low plasma arginine concentrations in children with cerebral malaria and decreased nitric oxide production","volume":"361","year":"2003","journal-title":"The Lancet"},{"key":"2023051820401209000_2023.05.16.540951v1.21","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jis339"},{"key":"2023051820401209000_2023.05.16.540951v1.22","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1008930"},{"key":"2023051820401209000_2023.05.16.540951v1.23","doi-asserted-by":"crossref","unstructured":"Gupta S , Seydel K , Miranda-Roman MA , et al. Extensive alterations of blood metabolites in pediatric cerebral malaria. PLoS ONE. 2017;12(4):.","DOI":"10.1371\/journal.pone.0175686"},{"key":"2023051820401209000_2023.05.16.540951v1.24","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1715971"},{"issue":"Supplement_1","key":"2023051820401209000_2023.05.16.540951v1.25","doi-asserted-by":"crossref","first-page":"3567","DOI":"10.1182\/blood-2019-128891","article-title":"Rheological Effects of L-Glutamine in Patients with Sickle Cell Disease","volume":"134","year":"2019","journal-title":"Blood"},{"issue":"1","key":"2023051820401209000_2023.05.16.540951v1.26","doi-asserted-by":"crossref","first-page":"570","DOI":"10.2119\/molmed.2016.00130","article-title":"Reduced Hsp70 and Glutamine in Pediatric Severe Malaria Anemia: Role of hemozoin in Suppressing Hsp70 and NF-\u03baB Activation","volume":"22","year":"2016","journal-title":"Molecular Medicine"},{"key":"2023051820401209000_2023.05.16.540951v1.27","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2006-09-048728"},{"issue":"4","key":"2023051820401209000_2023.05.16.540951v1.28","doi-asserted-by":"crossref","first-page":"617","DOI":"10.4269\/ajtmh.2007.77.617","article-title":"Effects of malaria heme products on red blood cell deformability","volume":"77","year":"2007","journal-title":"American Journal of Tropical Medicine and Hygiene"},{"key":"2023051820401209000_2023.05.16.540951v1.29","doi-asserted-by":"publisher","DOI":"10.1172\/JCI112196"},{"key":"2023051820401209000_2023.05.16.540951v1.30","doi-asserted-by":"publisher","DOI":"10.1016\/j.exppara.2006.12.003"},{"key":"2023051820401209000_2023.05.16.540951v1.31","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1007\/978-1-4939-7253-1_31","article-title":"Production and Characterization of Extracellular Vesicles in Malaria","volume":"1660","year":"2017","journal-title":"Extracellular Vesicles"},{"key":"2023051820401209000_2023.05.16.540951v1.32","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.2019"},{"key":"2023051820401209000_2023.05.16.540951v1.33","doi-asserted-by":"crossref","unstructured":"Colvin HN, Marrs , Glen, Cordy , Regina Joice . Osmolality-controlled fixation and simple preparation of human red blood cells for scanning electron microscopy . protocols.io. 2022;","DOI":"10.17504\/protocols.io.36wgq7xj5vk5\/v1"},{"issue":"4","key":"2023051820401209000_2023.05.16.540951v1.34","doi-asserted-by":"crossref","first-page":"e0215447","DOI":"10.1371\/journal.pone.0215447","article-title":"A coarse-grained red blood cell membrane model to study stomatocyte-discocyte-echinocyte morphologies","volume":"14","year":"2019","journal-title":"PLoS ONE"},{"issue":"1","key":"2023051820401209000_2023.05.16.540951v1.35","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1186\/s12958-019-0513-8","article-title":"Endometrium and endometriosis tissue mitochondrial energy metabolism in a nonhuman primate model","volume":"17","year":"2019","journal-title":"Reprod Biol Endocrinol"},{"issue":"7","key":"2023051820401209000_2023.05.16.540951v1.36","doi-asserted-by":"crossref","first-page":"292","DOI":"10.3390\/metabo10070292","article-title":"Optimized Protocol for the In Situ Derivatization of Glutathione with N-Ethylmaleimide in Cultured Cells and the Simultaneous Determination of Glutathione\/Glutathione Disulfide Ratio by HPLC-UV-QTOF-MS","volume":"10","year":"2020","journal-title":"Metabolites"},{"issue":"4","key":"2023051820401209000_2023.05.16.540951v1.37","first-page":"535","article-title":"Use of ektacytometry to determine red cell susceptibility to oxidative stress","volume":"116","year":"1990","journal-title":"J Lab Clin Med"},{"key":"2023051820401209000_2023.05.16.540951v1.38","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V61.5.899.899"},{"issue":"11\u201312","key":"2023051820401209000_2023.05.16.540951v1.39","first-page":"S48","article-title":"Transport of amino acids for glutathione biosynthesis in human and dog red cells","volume":"42","year":"1983","journal-title":"Biomed Biochim Acta"},{"key":"2023051820401209000_2023.05.16.540951v1.40","doi-asserted-by":"publisher","DOI":"10.1590\/S0100-879X2003000200002"},{"issue":"9","key":"2023051820401209000_2023.05.16.540951v1.41","doi-asserted-by":"crossref","first-page":"2582","DOI":"10.3390\/ijms19092582","article-title":"Identification of Oxidative Stress in Red Blood Cells with Nanoscale Chemical Resolution by Infrared Nanospectroscopy","volume":"19","year":"2018","journal-title":"IJMS"},{"issue":"1","key":"2023051820401209000_2023.05.16.540951v1.42","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1016\/0011-2240(83)90056-1","article-title":"Morphology of glutaraldehyde-fixed preserved red blood cells and 24-hr post-transfusion survival","volume":"20","year":"1983","journal-title":"Cryobiology"},{"key":"2023051820401209000_2023.05.16.540951v1.43","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/B978-0-12-005214-1.50006-6","article-title":"The Structure of Normal and Pathologic Erythrocytes","volume":"14","year":"1973","journal-title":"Advances in Biological and Medical Physics"},{"issue":"5","key":"2023051820401209000_2023.05.16.540951v1.44","doi-asserted-by":"crossref","first-page":"446","DOI":"10.1089\/rej.2014.1573","article-title":"Markers of Oxidative Stress in Senescent Erythrocytes Obtained from Young and Old Age Rats","volume":"17","year":"2014","journal-title":"Rejuvenation Research"},{"issue":"4","key":"2023051820401209000_2023.05.16.540951v1.45","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1016\/0300-9629(94)90329-8","article-title":"Amino acid transport by human erythrocyte membranes","volume":"108","year":"1994","journal-title":"Comparative Biochemistry and Physiology Part A: Physiology"},{"key":"2023051820401209000_2023.05.16.540951v1.46","unstructured":"Zolla L , D\u2019Alessandro A . Classic and alternative red blood cell storage strategies: seven years of \u201c-omics\u201d investigations. Blood Transfusion. 2015;"},{"key":"2023051820401209000_2023.05.16.540951v1.47","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M109.067017"},{"issue":"17","key":"2023051820401209000_2023.05.16.540951v1.48","doi-asserted-by":"crossref","first-page":"3152","DOI":"10.1111\/j.1742-4658.2011.08241.x","article-title":"Glutamine and \u03b1-ketoglutarate as glutamate sources for glutathione synthesis in human erythrocytes: Glutamate sources for glutathione synthesis","volume":"278","year":"2011","journal-title":"FEBS Journal"}],"container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1101\/2023.05.16.540951","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T04:39:58Z","timestamp":1768451998000},"score":1,"resource":{"primary":{"URL":"http:\/\/biorxiv.org\/lookup\/doi\/10.1101\/2023.05.16.540951"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,5,16]]},"references-count":48,"URL":"https:\/\/doi.org\/10.1101\/2023.05.16.540951","relation":{"is-preprint-of":[{"id-type":"doi","id":"10.1182\/bloodadvances.2023010820","asserted-by":"subject"}]},"subject":[],"published":{"date-parts":[[2023,5,16]]},"subtype":"preprint"}}