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Here, we show that L-arginine (Arg) uptake through the host cell\u2019s <jats:italic>SLC7A2<\/jats:italic>-encoded transporters is essential for the parasite\u2019s development and maturation in the liver. Our data suggest that the Arg that is taken up is primarily metabolized by the arginase pathway to produce the polyamines required for <jats:italic>Plasmodium<\/jats:italic> growth. Although the parasite may hijack the host\u2019s biosynthesis pathway, it relies mainly upon its own arginase-AdoMetDC\/ODC pathway to acquire the polyamines it needs to develop. These results identify for the first time a pivotal role for Arg-dependent polyamine production during <jats:italic>Plasmodium<\/jats:italic>\u2019s hepatic development and pave the way to the exploitation of strategies to impact liver infection by the malaria parasite through the modulation of Arg uptake and polyamine synthesis.<\/jats:p>","DOI":"10.1038\/s41598-017-04424-y","type":"journal-article","created":{"date-parts":[[2017,6,16]],"date-time":"2017-06-16T11:54:37Z","timestamp":1497614077000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["Uptake and metabolism of arginine impact Plasmodium development in the liver"],"prefix":"10.1038","volume":"7","author":[{"given":"Patr\u00edcia","family":"Meireles","sequence":"first","affiliation":[]},{"given":"Ant\u00f3nio M.","family":"Mendes","sequence":"additional","affiliation":[]},{"given":"Rita I.","family":"Aroeira","sequence":"additional","affiliation":[]},{"given":"Bryan C.","family":"Mounce","sequence":"additional","affiliation":[]},{"given":"Marco","family":"Vignuzzi","sequence":"additional","affiliation":[]},{"given":"Henry M.","family":"Staines","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1746-6029","authenticated-orcid":false,"given":"Miguel","family":"Prud\u00eancio","sequence":"additional","affiliation":[]}],"member":"297","published-online":{"date-parts":[[2017,6,22]]},"reference":[{"key":"4424_CR1","doi-asserted-by":"publisher","first-page":"849","DOI":"10.1038\/nrmicro1529","volume":"4","author":"M Prudencio","year":"2006","unstructured":"Prudencio, M., Rodriguez, A. & Mota, M. M. The silent path to thousands of merozoites: the Plasmodium liver stage. Nat Rev Microbiol \n                           4, 849\u2013856, doi:10.1038\/nrmicro1529 (2006).","journal-title":"Nat Rev Microbiol"},{"key":"4424_CR2","doi-asserted-by":"publisher","first-page":"995","DOI":"10.1021\/jm201095h","volume":"55","author":"T Rodrigues","year":"2012","unstructured":"Rodrigues, T., Prudencio, M., Moreira, R., Mota, M. M. & Lopes, F. Targeting the liver stage of malaria parasites: a yet unmet goal. J Med Chem \n                           55, 995\u20131012, doi:10.1021\/jm201095h (2012).","journal-title":"J Med Chem"},{"key":"4424_CR3","doi-asserted-by":"publisher","first-page":"565","DOI":"10.1016\/j.pt.2011.09.004","volume":"27","author":"M Prudencio","year":"2011","unstructured":"Prudencio, M., Mota, M. M. & Mendes, A. M. A toolbox to study liver stage malaria. 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Mol Aspects Med \n                           34, 139\u2013158, doi:10.1016\/j.mam.2012.10.007 (2013).","journal-title":"Mol Aspects Med"},{"key":"4424_CR6","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1007\/s00232-006-0875-7","volume":"213","author":"EI Closs","year":"2006","unstructured":"Closs, E. I., Boissel, J. P., Habermeier, A. & Rotmann, A. Structure and function of cationic amino acid transporters (CATs). J Membr Biol \n                           213, 67\u201377, doi:10.1007\/s00232-006-0875-7 (2006).","journal-title":"J Membr Biol"},{"key":"4424_CR7","doi-asserted-by":"publisher","first-page":"6462","DOI":"10.1021\/bi962829p","volume":"36","author":"EI Closs","year":"1997","unstructured":"Closs, E. I., Graf, P., Habermeier, A., Cunningham, J. M. & Forstermann, U. Human cationic amino acid transporters hCAT-1, hCAT-2A, and hCAT-2B: three related carriers with distinct transport properties. Biochemistry \n                           36, 6462\u20136468, doi:10.1021\/bi962829p (1997).","journal-title":"Biochemistry"},{"key":"4424_CR8","doi-asserted-by":"crossref","first-page":"7538","DOI":"10.1016\/S0021-9258(18)53209-9","volume":"268","author":"EI Closs","year":"1993","unstructured":"Closs, E. I., Albritton, L. M., Kim, J. W. & Cunningham, J. M. Identification of a low affinity, high capacity transporter of cationic amino acids in mouse liver. J Biol Chem \n                           268, 7538\u20137544 (1993).","journal-title":"J Biol Chem"},{"key":"4424_CR9","doi-asserted-by":"publisher","first-page":"725","DOI":"10.1038\/352725a0","volume":"352","author":"JW Kim","year":"1991","unstructured":"Kim, J. W., Closs, E. I., Albritton, L. M. & Cunningham, J. M. Transport of cationic amino acids by the mouse ecotropic retrovirus receptor. 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