{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T02:44:50Z","timestamp":1790909090017,"version":"4.1.0"},"reference-count":131,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2021,12,15]],"date-time":"2021-12-15T00:00:00Z","timestamp":1639526400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["2R01AI120607-06A1"],"award-info":[{"award-number":["2R01AI120607-06A1"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Microorganisms"],"abstract":"<jats:p>Obligate intracellular parasites have evolved a remarkable assortment of strategies to scavenge nutrients from the host cells they parasitize. Most apicomplexans form a parasitophorous vacuole (PV) within the invaded cell, a replicative niche within which they survive and multiply. As well as providing a physical barrier against host cell defense mechanisms, the PV membrane (PVM) is also an important site of nutrient uptake that is essential for the parasites to sustain their metabolism. This means nutrients in the extracellular milieu are separated from parasite metabolic machinery by three different membranes, the host plasma membrane, the PVM, and the parasite plasma membrane (PPM). In order to facilitate nutrient transport from the extracellular environment into the parasite itself, transporters on the host cell membrane of invaded cells can be modified by secreted and exported parasite proteins to maximize uptake of key substrates to meet their metabolic demand. To overcome the second barrier, the PVM, apicomplexan parasites secrete proteins contained in the dense granules that remodel the vacuole and make the membrane permissive to important nutrients. This bulk flow of host nutrients is followed by a more selective uptake of substrates at the PPM that is operated by specific transporters of this third barrier. In this review, we recapitulate and compare the strategies developed by Apicomplexa to scavenge nutrients from their hosts, with particular emphasis on transporters at the parasite plasma membrane and vacuolar solute transporters on the parasite intracellular digestive organelle.<\/jats:p>","DOI":"10.3390\/microorganisms9122592","type":"journal-article","created":{"date-parts":[[2021,12,15]],"date-time":"2021-12-15T21:47:36Z","timestamp":1639604856000},"page":"2592","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["An Uninvited Seat at the Dinner Table: How Apicomplexan Parasites Scavenge Nutrients from the Host"],"prefix":"10.3390","volume":"9","author":[{"given":"Federica","family":"Piro","sequence":"first","affiliation":[{"name":"Department of Chemistry, Biology and Biotechnology, University of Perugia, 06122 Perugia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Riccardo","family":"Focaia","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Biology and Biotechnology, University of Perugia, 06122 Perugia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhicheng","family":"Dou","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, Clemson University, Clemson, SC 29634, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia","family":"Masci","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Biology and Biotechnology, University of Perugia, 06122 Perugia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Smith","sequence":"additional","affiliation":[{"name":"Department of Disease Control, Moredun Research Institute, Midlothian EH26 0PZ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4154-5210","authenticated-orcid":false,"given":"Manlio","family":"Di Cristina","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Biology and Biotechnology, University of Perugia, 06122 Perugia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,12,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"684","DOI":"10.1080\/10635150701494127","article-title":"Diversity, Nomenclature, and Taxonomy of Protists","volume":"56","author":"Adl","year":"2007","journal-title":"Syst. Biol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"759","DOI":"10.1016\/j.pt.2018.07.006","article-title":"Apicomplexa Cell Cycles: Something Old, Borrowed, Lost, and New","volume":"34","author":"White","year":"2018","journal-title":"Trends Parasitol."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Striepen, B., Jordan, C.N., Reiff, S., and van Dooren, G.G. (2007). Building the Perfect Parasite: Cell Division in Apicomplexa. PLoS Pathog., 3.","DOI":"10.1371\/journal.ppat.0030078"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"520","DOI":"10.1016\/j.pt.2020.03.010","article-title":"Endocytosis in Plasmodium and Toxoplasma Parasites","volume":"36","author":"Spielmann","year":"2020","journal-title":"Trends Parasitol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1016\/j.chom.2020.09.007","article-title":"The Biology of the Intestinal Intracellular Parasite Cryptosporidium","volume":"28","author":"Striepen","year":"2020","journal-title":"Cell Host Microbe"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"588","DOI":"10.1186\/s13071-020-04445-z","article-title":"The Life-Cycle of Toxoplasma gondii Reviewed Using Animations","volume":"13","author":"Attias","year":"2020","journal-title":"Parasit Vectors"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1016\/j.tem.2013.01.002","article-title":"Nutrient Transporters: The Achilles\u2019 Heel of Anabolism","volume":"24","author":"McCracken","year":"2013","journal-title":"Trends Endocrinol. Metab."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1242\/jeb.196.1.15","article-title":"Structure, Function and Evolution of Solute Transporters in Prokaryotes and Eukaryotes","volume":"196","author":"Hediger","year":"1994","journal-title":"J. Exp. Biol."},{"key":"ref_9","first-page":"S397","article-title":"THE CONCISE GUIDE TO PHARMACOLOGY 2019\/20: Transporters","volume":"176","author":"Alexander","year":"2019","journal-title":"Br. J. Pharm."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1038\/aps.2013.142","article-title":"Deorphanizing the Human Transmembrane Genome: A Landscape of Uncharacterized Membrane Proteins","volume":"35","author":"Babcock","year":"2014","journal-title":"Acta Pharm. Sin."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1069","DOI":"10.1039\/C6MD00005C","article-title":"SLC Transporters: Structure, Function, and Drug Discovery","volume":"7","author":"Colas","year":"2016","journal-title":"Medchemcomm"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1007","DOI":"10.1016\/S0022-2275(20)31588-1","article-title":"The Human ATP-Binding Cassette (ABC) Transporter Superfamily","volume":"42","author":"Dean","year":"2001","journal-title":"J. Lipid Res."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1007\/s00424-003-1192-y","article-title":"The ABCs of Solute Carriers: Physiological, Pathological and Therapeutic Implications of Human Membrane Transport Proteins Introduction","volume":"447","author":"Hediger","year":"2004","journal-title":"Pflug. Arch."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1080\/10409230290771528","article-title":"The Transporter Classification (TC) System, 2002","volume":"37","author":"Busch","year":"2002","journal-title":"Crit. Rev. Biochem. Mol. Biol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"853","DOI":"10.1124\/jpet.103.059972","article-title":"Structures and Models of Transporter Proteins","volume":"309","author":"Dahl","year":"2004","journal-title":"J. Pharm. Exp."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1016\/j.mam.2012.12.009","article-title":"The ABCs of Membrane Transporters in Health and Disease (SLC Series): Introduction","volume":"34","author":"Hediger","year":"2013","journal-title":"Mol. Asp. Med."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1038\/nrm2646","article-title":"ABC Transporters: The Power to Change","volume":"10","author":"Rees","year":"2009","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"605","DOI":"10.1146\/annurev-biochem-011520-105201","article-title":"Structural and Mechanistic Principles of ABC Transporters","volume":"89","author":"Thomas","year":"2020","journal-title":"Annu. Rev. Biochem."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"261","DOI":"10.2183\/pjab.95.018","article-title":"Vacuolar-Type ATPase: A Proton Pump to Lysosomal Trafficking","volume":"95","author":"Futai","year":"2019","journal-title":"Proc. Jpn. Acad. Ser. B Phys. Biol. Sci."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"957","DOI":"10.1038\/450957a","article-title":"Structural Biology: Ion Pumps Made Crystal Clear","volume":"450","author":"Gadsby","year":"2007","journal-title":"Nature"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"8743257","DOI":"10.1155\/2019\/8743257","article-title":"Mitochondrial F-ATP Synthase and Its Transition into an Energy-Dissipating Molecular Machine","volume":"2019","author":"Lippe","year":"2019","journal-title":"Oxid. Med. Cell. Longev."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1146\/annurev.biophys.093008.131331","article-title":"P-Type ATPases","volume":"40","author":"Palmgren","year":"2011","journal-title":"Annu. Rev. Biophys."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"314","DOI":"10.1016\/0014-5793(90)81278-V","article-title":"The Fourth Datta Lecture. The Energy Coupled Exchange of Na+ for K+ across the Cell Membrane. The Na+, K+-Pump","volume":"268","author":"Skou","year":"1990","journal-title":"FEBS Lett."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1080\/09687688.2018.1448123","article-title":"Structural Biology of Solute Carrier (SLC) Membrane Transport Proteins","volume":"34","author":"Bai","year":"2017","journal-title":"Mol. Membr. Biol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1146\/annurev-biophys-083012-130429","article-title":"Common Folds and Transport Mechanisms of Secondary Active Transporters","volume":"42","author":"Shi","year":"2013","journal-title":"Annu. Rev. Biophys."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1093\/jmcb\/mjy052","article-title":"The SLC Transporter in Nutrient and Metabolic Sensing, Regulation, and Drug Development","volume":"11","author":"Zhang","year":"2019","journal-title":"J. Mol. Cell Biol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1016\/j.tips.2016.11.008","article-title":"Classification Systems of Secondary Active Transporters","volume":"38","author":"Perland","year":"2017","journal-title":"Trends Pharm. Sci."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1007\/s00424-002-0840-y","article-title":"Adaptation of Plasma Membrane Amino Acid Transport Mechanisms to Physiological Demands","volume":"444","year":"2002","journal-title":"Pflug. Arch."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"678","DOI":"10.1007\/s00439-001-0615-0","article-title":"The HUGO Gene Nomenclature Committee (HGNC)","volume":"109","author":"Povey","year":"2001","journal-title":"Hum. Genet."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1146\/annurev-biophys-051013-023008","article-title":"Structural Symmetry in Membrane Proteins","volume":"44","author":"Forrest","year":"2015","journal-title":"Annu. Rev. Biophys."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"5289","DOI":"10.1021\/acs.chemrev.0c00983","article-title":"Structures and General Transport Mechanisms by the Major Facilitator Superfamily (MFS)","volume":"121","author":"Drew","year":"2021","journal-title":"Chem. Rev."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1016\/j.jsb.2007.01.011","article-title":"Discontinuous Membrane Helices in Transport Proteins and Their Correlation with Function","volume":"159","author":"Screpanti","year":"2007","journal-title":"J. Struct. Biol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1146\/annurev-biophys-060414-033901","article-title":"Structural Biology of the Major Facilitator Superfamily Transporters","volume":"44","author":"Yan","year":"2015","journal-title":"Annu. Rev. Biophys."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"(2019). UniProt Consortium UniProt: A Worldwide Hub of Protein Knowledge. Nucleic Acids Res., 47, D506\u2013D515.","DOI":"10.1093\/nar\/gky1049"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1242\/jeb.196.1.93","article-title":"Na+-Independent Transport (Uniport) of Amino Acids and Glucose in Mammalian Cells","volume":"196","author":"Kakuda","year":"1994","journal-title":"J. Exp. Biol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1016\/j.pt.2017.02.007","article-title":"The Toxoplasma Parasitophorous Vacuole: An Evolving Host-Parasite Frontier","volume":"33","author":"Clough","year":"2017","journal-title":"Trends Parasitol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1016\/j.pt.2019.11.006","article-title":"Hardly Vacuous: The Parasitophorous Vacuolar Membrane of Malaria Parasites","volume":"36","author":"Goldberg","year":"2020","journal-title":"Trends Parasitol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"248","DOI":"10.3389\/fcimb.2018.00248","article-title":"The Complexity of Piroplasms Life Cycles","volume":"8","author":"Jalovecka","year":"2018","journal-title":"Front. Cell Infect. Microbiol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1003","DOI":"10.1111\/j.1462-5822.2012.01790.x","article-title":"Ion and Nutrient Uptake by Malaria Parasite-Infected Erythrocytes","volume":"14","author":"Desai","year":"2012","journal-title":"Cell Microbiol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1001","DOI":"10.1038\/35023000","article-title":"A Voltage-Dependent Channel Involved in Nutrient Uptake by Red Blood Cells Infected with the Malaria Parasite","volume":"406","author":"Desai","year":"2000","journal-title":"Nature"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1002\/jcp.1041140215","article-title":"Permselectivity Changes in Malaria (Plasmodium falciparum) Infected Human Red Blood Cell Membranes","volume":"114","author":"Kutner","year":"1983","journal-title":"J. Cell Physiol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"665","DOI":"10.1016\/j.cell.2011.05.002","article-title":"Malaria Parasite Clag3 Genes Determine Channel-Mediated Nutrient Uptake by Infected Red Blood Cells","volume":"145","author":"Nguitragool","year":"2011","journal-title":"Cell"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"649184","DOI":"10.3389\/fcell.2021.649184","article-title":"How Malaria Parasites Acquire Nutrients from Their Host","volume":"9","author":"Counihan","year":"2021","journal-title":"Front. Cell Dev. Biol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"3429","DOI":"10.1007\/s00436-019-06471-y","article-title":"Cryptosporidium Parvum Alters Glucose Transport Mechanisms in Infected Enterocytes","volume":"118","author":"Delling","year":"2019","journal-title":"Parasitol. Res."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1090","DOI":"10.1038\/s41564-018-0222-7","article-title":"EXP2 Is a Nutrient-Permeable Channel in the Vacuolar Membrane of Plasmodium and Is Essential for Protein Export via PTEX","volume":"3","author":"Garten","year":"2018","journal-title":"Nat. Microbiol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"642","DOI":"10.1016\/j.chom.2015.04.003","article-title":"The Toxoplasma Dense Granule Proteins GRA17 and GRA23 Mediate the Movement of Small Molecules between the Host and the Parasitophorous Vacuole","volume":"17","author":"Gold","year":"2015","journal-title":"Cell Host Microbe"},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Mes\u00e9n-Ram\u00edrez, P., Bergmann, B., Tran, T.T., Garten, M., St\u00e4cker, J., Naranjo-Prado, I., H\u00f6hn, K., Zimmerberg, J., and Spielmann, T. (2019). EXP1 Is Critical for Nutrient Uptake across the Parasitophorous Vacuole Membrane of Malaria Parasites. PLoS Biol., 17.","DOI":"10.1371\/journal.pbio.3000473"},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Mes\u00e9n-Ram\u00edrez, P., Reinsch, F., Blancke Soares, A., Bergmann, B., Ullrich, A.-K., Tenzer, S., and Spielmann, T. (2016). Stable Translocation Intermediates Jam Global Protein Export in Plasmodium falciparum Parasites and Link the PTEX Component EXP2 with Translocation Activity. PLoS Pathog., 12.","DOI":"10.1371\/journal.ppat.1005618"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1111\/mmi.12206","article-title":"Robust Inducible Cre Recombinase Activity in the Human Malaria Parasite Plasmodium falciparum Enables Efficient Gene Deletion within a Single Asexual Erythrocytic Growth Cycle","volume":"88","author":"Collins","year":"2013","journal-title":"Mol. Microbiol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"916","DOI":"10.1016\/j.cell.2014.07.011","article-title":"Supergenomic Network Compression and the Discovery of EXP1 as a Glutathione Transferase Inhibited by Artesunate","volume":"158","author":"Lisewski","year":"2014","journal-title":"Cell"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1329","DOI":"10.1016\/j.ijpara.2007.04.005","article-title":"Cellular Interactions of Plasmodium Liver Stage with Its Host Mammalian Cell","volume":"37","author":"Bano","year":"2007","journal-title":"Int. J. Parasitol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"3618","DOI":"10.1172\/JCI62684","article-title":"Complete Plasmodium falciparum Liver-Stage Development in Liver-Chimeric Mice","volume":"122","author":"Vaughan","year":"2012","journal-title":"J. Clin. Investig."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"567","DOI":"10.1146\/annurev-micro-011720-122318","article-title":"Toxoplasma Mechanisms for Delivery of Proteins and Uptake of Nutrients Across the Host-Pathogen Interface","volume":"74","author":"Wang","year":"2020","journal-title":"Annu. Rev. Microbiol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"321","DOI":"10.3389\/fcimb.2019.00321","article-title":"The GRA17 Parasitophorous Vacuole Membrane Permeability Pore Contributes to Bradyzoite Viability","volume":"9","author":"Wang","year":"2019","journal-title":"Front. Cell Infect. Microbiol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1007\/s00018-007-7434-y","article-title":"Bacterial Pore-Forming Toxins: The (w)Hole Story?","volume":"65","author":"Gonzalez","year":"2008","journal-title":"Cell Mol. Life Sci."},{"key":"ref_56","first-page":"1424","article-title":"The Malaria Digestive Vacuole","volume":"4","author":"Wunderlich","year":"2012","journal-title":"Front. Biosci."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1016\/j.ijpara.2010.09.001","article-title":"Methionine Transport in the Malaria Parasite Plasmodium falciparum","volume":"41","author":"Cobbold","year":"2011","journal-title":"Int. J. Parasitol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"2217","DOI":"10.1182\/blood-2005-11-026963","article-title":"Transport of the Essential Nutrient Isoleucine in Human Erythrocytes Infected with the Malaria Parasite Plasmodium falciparum","volume":"109","author":"Martin","year":"2007","journal-title":"Blood"},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"McGovern, O.L., Rivera-Cuevas, Y., and Carruthers, V.B. (2021). Emerging Mechanisms of Endocytosis in Toxoplasma gondii. Life, 11.","DOI":"10.3390\/life11020084"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1016\/j.cell.2006.01.056","article-title":"Toxoplasma gondii Sequesters Lysosomes from Mammalian Hosts in the Vacuolar Space","volume":"125","author":"Coppens","year":"2006","journal-title":"Cell"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1232","DOI":"10.1111\/j.1365-2958.2010.07169.x","article-title":"Novel Roles for ATP-Binding Cassette G Transporters in Lipid Redistribution in Toxoplasma","volume":"76","author":"Ehrenman","year":"2010","journal-title":"Mol. Microbiol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"12998","DOI":"10.1073\/pnas.0903831106","article-title":"Host-Derived Glucose and Its Transporter in the Obligate Intracellular Pathogen Toxoplasma gondii Are Dispensable by Glutaminolysis","volume":"106","author":"Blume","year":"2009","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"7272","DOI":"10.1074\/jbc.274.11.7272","article-title":"Intraerythrocytic Plasmodium falciparum Expresses a High Affinity Facilitative Hexose Transporter","volume":"274","author":"Woodrow","year":"1999","journal-title":"J. Biol. Chem."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"10683","DOI":"10.1074\/jbc.275.14.10683","article-title":"Isolation and Functional Characterization of the PfNT1 Nucleoside Transporter Gene from Plasmodium falciparum","volume":"275","author":"Carter","year":"2000","journal-title":"J. Biol. Chem."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1042\/bj3490067","article-title":"Identification of a Nucleoside\/Nucleobase Transporter from Plasmodium falciparum, a Novel Target for Anti-Malarial Chemotherapy","volume":"349","author":"Parker","year":"2000","journal-title":"Biochem. J."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"20827","DOI":"10.1074\/jbc.M110.118489","article-title":"PfNT2, a Permease of the Equilibrative Nucleoside Transporter Family in the Endoplasmic Reticulum of Plasmodium falciparum","volume":"285","author":"Downie","year":"2010","journal-title":"J. Biol. Chem."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1016\/j.ijpara.2007.07.005","article-title":"Purine Nucleobase Transport in the Intraerythrocytic Malaria Parasite","volume":"38","author":"Downie","year":"2008","journal-title":"Int. J. Parasitol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"738","DOI":"10.1111\/j.1365-2958.2006.05125.x","article-title":"Transport of Nucleosides across the Plasmodium falciparum Parasite Plasma Membrane Has Characteristics of PfENT1","volume":"60","author":"Downie","year":"2006","journal-title":"Mol. Microbiol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"35255","DOI":"10.1074\/jbc.274.49.35255","article-title":"The Adenosine Transporter of Toxoplasma gondii Identification by Insertional Mutagenesis, Cloning, and Recombinant Expression","volume":"274","author":"Chiang","year":"1999","journal-title":"J. Biol. Chem."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"e0074321","DOI":"10.1128\/mSphere.00743-21","article-title":"Characterization of Apicomplexan Amino Acid Transporters (ApiATs) in the Malaria Parasite Plasmodium falciparum","volume":"6","author":"Wichers","year":"2021","journal-title":"mSphere"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"14455","DOI":"10.1038\/ncomms14455","article-title":"Cationic Amino Acid Transporters Play Key Roles in the Survival and Transmission of Apicomplexan Parasites","volume":"8","author":"Rajendran","year":"2017","journal-title":"Nat. Commun."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1343","DOI":"10.1111\/j.1365-2958.2011.07767.x","article-title":"The Novel Putative Transporter NPT1 Plays a Critical Role in Early Stages of Plasmodium berghei Sexual Development","volume":"81","author":"Boisson","year":"2011","journal-title":"Mol. Microbiol."},{"key":"ref_73","doi-asserted-by":"crossref","unstructured":"Parker, K.E.R., Fairweather, S.J., Rajendran, E., Blume, M., McConville, M.J., Br\u00f6er, S., Kirk, K., and van Dooren, G.G. (2019). The Tyrosine Transporter of Toxoplasma gondii Is a Member of the Newly Defined Apicomplexan Amino Acid Transporter (ApiAT) Family. PLoS Pathog., 15.","DOI":"10.1371\/journal.ppat.1007577"},{"key":"ref_74","doi-asserted-by":"crossref","unstructured":"Rajendran, E., Clark, M., Goulart, C., Steinh\u00f6fel, B., Tjhin, E.T., Gross, S., Smith, N.C., Kirk, K., and van Dooren, G.G. (2021). Substrate-Mediated Regulation of the Arginine Transporter of Toxoplasma gondii. PLoS Pathog., 17.","DOI":"10.1371\/journal.ppat.1009816"},{"key":"ref_75","doi-asserted-by":"crossref","unstructured":"Fairweather, S.J., Rajendran, E., Blume, M., Javed, K., Steinh\u00f6fel, B., McConville, M.J., Kirk, K., Br\u00f6er, S., and van Dooren, G.G. (2021). Coordinated Action of Multiple Transporters in the Acquisition of Essential Cationic Amino Acids by the Intracellular Parasite Toxoplasma gondii. PLoS Pathog., 17.","DOI":"10.1101\/2021.06.25.450001"},{"key":"ref_76","doi-asserted-by":"crossref","unstructured":"Kloehn, J., Lunghi, M., Varesio, E., Dubois, D., and Soldati-Favre, D. (2021). Untargeted Metabolomics Uncovers the Essential Lysine Transporter in Toxoplasma gondii. Metabolites, 11.","DOI":"10.3390\/metabo11080476"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1111\/brv.12565","article-title":"The Transportome of the Malaria Parasite","volume":"95","author":"Martin","year":"2020","journal-title":"Biol. Camb. Philos."},{"key":"ref_78","first-page":"861","article-title":"Mutations in the P. Falciparum Digestive Vacuole Transmembrane Protein PfCRT and Evidence for Their Role in Chloroquine Resistance","volume":"6","author":"Fidock","year":"2000","journal-title":"Cell"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"1680","DOI":"10.1126\/science.1175667","article-title":"Chloroquine Transport via the Malaria Parasite\u2019s Chloroquine Resistance Transporter","volume":"325","author":"Martin","year":"2009","journal-title":"Science"},{"key":"ref_80","doi-asserted-by":"crossref","unstructured":"Thornton, L.B., Teehan, P., Floyd, K., Cochrane, C., Bergmann, A., Riegel, B., Stasic, A.J., Di Cristina, M., Moreno, S.N.J., and Roepe, P.D. (2019). An Ortholog of Plasmodium falciparum Chloroquine Resistance Transporter (PfCRT) Plays a Key Role in Maintaining the Integrity of the Endolysosomal System in Toxoplasma gondii to Facilitate Host Invasion. PLoS Pathog., 15.","DOI":"10.1371\/journal.ppat.1007775"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"e01324-19","DOI":"10.1128\/mBio.01324-19","article-title":"Role of Toxoplasma gondii Chloroquine Resistance Transporter in Bradyzoite Viability and Digestive Vacuole Maintenance","volume":"10","author":"Kannan","year":"2019","journal-title":"mBio"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"1360","DOI":"10.1128\/EC.00027-14","article-title":"Characterization of the Chloroquine Resistance Transporter Homologue in Toxoplasma gondii","volume":"13","author":"Warring","year":"2014","journal-title":"Eukaryot. Cell"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"52300","DOI":"10.1074\/jbc.M409175200","article-title":"The Expression of Lactate Dehydrogenase Is Important for the Cell Cycle of Toxoplasma gondii","volume":"279","author":"Tomavo","year":"2004","journal-title":"J. Biol. Chem."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"682","DOI":"10.1016\/j.chom.2012.09.013","article-title":"Mitochondrial Metabolism of Glucose and Glutamine Is Required for Intracellular Growth of Toxoplasma gondii","volume":"12","author":"MacRae","year":"2012","journal-title":"Cell Host Microbe"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"1321","DOI":"10.1016\/S0020-7519(01)00258-2","article-title":"Nutrient Acquisition by Intracellular Apicomplexan Parasites: Staying in for Dinner","volume":"31","author":"Saliba","year":"2001","journal-title":"Int. J. Parasitol."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"3567","DOI":"10.1073\/pnas.1315156111","article-title":"Toxoplasma Aldolase Is Required for Metabolism but Dispensable for Host-Cell Invasion","volume":"111","author":"Shen","year":"2014","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_87","doi-asserted-by":"crossref","unstructured":"Pomel, S., Luk, F.C.Y., and Beckers, C.J.M. (2008). Host Cell Egress and Invasion Induce Marked Relocations of Glycolytic Enzymes in Toxoplasma gondii Tachyzoites. PLoS Pathog., 4.","DOI":"10.1371\/journal.ppat.1000188"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"955","DOI":"10.1016\/j.ijpara.2018.05.013","article-title":"Glycolysis Is Important for Optimal Asexual Growth and Formation of Mature Tissue Cysts by Toxoplasma gondii","volume":"48","author":"Shukla","year":"2018","journal-title":"Int. J. Parasitol."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1016\/0166-6851(96)02734-X","article-title":"Glucose Uptake in Plasmodium falciparum-Infected Erythrocytes Is an Equilibrative Not an Active Process","volume":"82","author":"Kirk","year":"1996","journal-title":"Mol. Biochem. Parasitol."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"1402","DOI":"10.1111\/j.1365-2958.2010.07060.x","article-title":"Life Cycle Studies of the Hexose Transporter of Plasmodium Species and Genetic Validation of Their Essentiality","volume":"75","author":"Slavic","year":"2010","journal-title":"Mol. Microbiol."},{"key":"ref_91","first-page":"453","article-title":"Plasmodium falciparum Carbohydrate Metabolism: A Connection between Host Cell and Parasite","volume":"16","author":"Roth","year":"1990","journal-title":"Blood Cells"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1038\/s41586-020-1963-z","article-title":"The Molecular Basis for Sugar Import in Malaria Parasites","volume":"578","author":"Qureshi","year":"2020","journal-title":"Nature"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"9931","DOI":"10.1073\/pnas.170153097","article-title":"Hexose Permeation Pathways in Plasmodium falciparum-Infected Erythrocytes","volume":"97","author":"Woodrow","year":"2000","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"2824","DOI":"10.1128\/AAC.01739-10","article-title":"Use of a Selective Inhibitor to Define the Chemotherapeutic Potential of the Plasmodial Hexose Transporter in Different Stages of the Parasite\u2019s Life Cycle","volume":"55","author":"Slavic","year":"2011","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_95","first-page":"1707231","article-title":"Evolution of the Apicomplexan Sugar Transporter Gene Family Repertoire","volume":"2017","author":"Mahmud","year":"2017","journal-title":"Int. J. Genom."},{"key":"ref_96","unstructured":"Sherman, I.W. (1998). Malaria: Parasite Biology, Pathogenesis, and Protection, Amer Society for Microbiology."},{"key":"ref_97","unstructured":"Marr, J.J., and M\u00fcller, M. (1995). 6\u2014Purine and Pyrimidine Metabolism. Biochemistry and Molecular Biology of Parasites, Academic Press."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"R26","DOI":"10.1186\/gb-2005-6-3-r26","article-title":"The \u201cpermeome\u201d of the Malaria Parasite: An Overview of the Membrane Transport Proteins of Plasmodium falciparum","volume":"6","author":"Martin","year":"2005","journal-title":"Genome Biol."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"17001","DOI":"10.1074\/jbc.M110.115758","article-title":"Transmembrane Segment 11 Appears to Line the Purine Permeation Pathway of the Plasmodium falciparum Equilibrative Nucleoside Transporter 1 (PfENT1)","volume":"285","author":"Riegelhaupt","year":"2010","journal-title":"J. Biol. Chem."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1016\/j.molbiopara.2009.10.001","article-title":"Transport of Purines and Purine Salvage Pathway Inhibitors by the Plasmodium falciparum Equilibrative Nucleoside Transporter PfENT1","volume":"169","author":"Riegelhaupt","year":"2010","journal-title":"Mol. Biochem. Parasitol."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"9286","DOI":"10.1073\/pnas.0602590103","article-title":"The Plasma Membrane Permease PfNT1 Is Essential for Purine Salvage in the Human Malaria Parasite Plasmodium falciparum","volume":"103","author":"Zufferey","year":"2006","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1016\/j.molbiopara.2008.06.012","article-title":"Genetic Evidence for the Essential Role of PfNT1 in the Transport and Utilization of Xanthine, Guanine, Guanosine and Adenine by Plasmodium falciparum","volume":"161","author":"Downie","year":"2008","journal-title":"Mol. Biochem. Parasitol."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1042\/BJ20071460","article-title":"A Comprehensive Model of Purine Uptake by the Malaria Parasite Plasmodium falciparum: Identification of Four Purine Transport Activities in Intraerythrocytic Parasites","volume":"411","author":"Quashie","year":"2008","journal-title":"Biochem. J."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1042\/BJ20112220","article-title":"Malaria Parasite Type 4 Equilibrative Nucleoside Transporters (ENT4) Are Purine Transporters with Distinct Substrate Specificity","volume":"446","author":"Frame","year":"2012","journal-title":"Biochem. J."},{"key":"ref_105","doi-asserted-by":"crossref","unstructured":"Cassera, M.B., Hazleton, K.Z., Merino, E.F., Obaldia, N., Ho, M.-C., Murkin, A.S., DePinto, R., Gutierrez, J.A., Almo, S.C., and Evans, G.B. (2011). Plasmodium falciparum Parasites Are Killed by a Transition State Analogue of Purine Nucleoside Phosphorylase in a Primate Animal Model. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0026916"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1111\/nyas.12568","article-title":"Purine Import into Malaria Parasites as a Target for Antimalarial Drug Development","volume":"1342","author":"Frame","year":"2015","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"31","DOI":"10.2174\/138945007779315524","article-title":"Targeting Purine and Pyrimidine Metabolism in Human Apicomplexan Parasites","volume":"8","author":"Hyde","year":"2007","journal-title":"Curr. Drug Targets"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"821","DOI":"10.1016\/S0020-7519(03)00091-2","article-title":"Identification and Characterisation of High Affinity Nucleoside and Nucleobase Transporters in Toxoplasma gondii","volume":"33","author":"Cohen","year":"2003","journal-title":"Int. J. Parasitol."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"11191","DOI":"10.1038\/ncomms11191","article-title":"Unconventional Endosome-like Compartment and Retromer Complex in Toxoplasma gondii Govern Parasite Integrity and Host Infection","volume":"7","author":"Alayi","year":"2016","journal-title":"Nat. Commun."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"1423","DOI":"10.1016\/j.cell.2016.08.019","article-title":"A Genome-Wide CRISPR Screen in Toxoplasma Identifies Essential Apicomplexan Genes","volume":"166","author":"Sidik","year":"2016","journal-title":"Cell"},{"key":"ref_111","doi-asserted-by":"crossref","unstructured":"Augusto, L., Amin, P.H., Wek, R.C., and Sullivan, W.J. (2019). Regulation of Arginine Transport by GCN2 EIF2 Kinase Is Important for Replication of the Intracellular Parasite Toxoplasma gondii. PLoS Pathog., 15.","DOI":"10.1371\/journal.ppat.1007746"},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"1167","DOI":"10.1111\/mmi.14156","article-title":"Characterisation of the Toxoplasma gondii Tyrosine Transporter and Its Phosphorylation by the Calcium-Dependent Protein Kinase 3","volume":"111","author":"Wallbank","year":"2019","journal-title":"Mol. Microbiol."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1111\/j.1550-7408.1985.tb03013.x","article-title":"Nutritional Requirements of Plasmodium falciparum in Culture. I. Exogenously Supplied Dialyzable Components Necessary for Continuous Growth","volume":"32","author":"Divo","year":"1985","journal-title":"J. Protozool."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"8840","DOI":"10.1073\/pnas.0601876103","article-title":"Plasmodium falciparum Ensures Its Amino Acid Supply with Multiple Acquisition Pathways and Redundant Proteolytic Enzyme Systems","volume":"103","author":"Liu","year":"2006","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"1549","DOI":"10.1016\/S0021-9258(19)83738-9","article-title":"The Structure of Human Hemoglobin. I. The Separation of the Alpha and Beta Chains and Their Amino Acid Composition","volume":"237","author":"Hill","year":"1962","journal-title":"J. Biol. Chem."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"10519","DOI":"10.1038\/ncomms10519","article-title":"Functional Profiles of Orphan Membrane Transporters in the Life Cycle of the Malaria Parasite","volume":"7","author":"Kenthirapalan","year":"2016","journal-title":"Nat. Commun."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1111\/j.1365-2958.2009.06863.x","article-title":"Membrane Transport Proteins of the Malaria Parasite","volume":"74","author":"Martin","year":"2009","journal-title":"Mol. Microbiol."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"eaap7847","DOI":"10.1126\/science.aap7847","article-title":"Uncovering the Essential Genes of the Human Malaria Parasite Plasmodium falciparum by Saturation Mutagenesis","volume":"360","author":"Zhang","year":"2018","journal-title":"Science"},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1093\/femsre\/fuz010","article-title":"Revisiting Gametocyte Biology in Malaria Parasites","volume":"43","author":"Ngotho","year":"2019","journal-title":"FEMS Microbiol."},{"key":"ref_120","doi-asserted-by":"crossref","unstructured":"B\u00e1rtfai, R., Hoeijmakers, W.A.M., Salcedo-Amaya, A.M., Smits, A.H., Janssen-Megens, E., Kaan, A., Treeck, M., Gilberger, T.-W., Fran\u00e7oijs, K.-J., and Stunnenberg, H.G. (2010). H2A.Z Demarcates Intergenic Regions of the Plasmodium falciparum Epigenome That Are Dynamically Marked by H3K9ac and H3K4me3. PLoS Pathog., 6.","DOI":"10.1371\/journal.ppat.1001223"},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1126\/science.aan4472","article-title":"Mapping the Malaria Parasite Druggable Genome by Using In Vitro Evolution and Chemogenomics","volume":"359","author":"Cowell","year":"2018","journal-title":"Science"},{"key":"ref_122","first-page":"12","article-title":"New Insights into the Blood-Stage Transcriptome of Plasmodium falciparum Using RNA-Seq","volume":"76","author":"Otto","year":"2010","journal-title":"Microbiology"},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"3356","DOI":"10.1073\/pnas.1417102112","article-title":"Plasmodium falciparum Chloroquine Resistance Transporter Is a H+-Coupled Polyspecific Nutrient and Drug Exporter","volume":"112","author":"Juge","year":"2015","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"3922","DOI":"10.1038\/s41467-020-17781-6","article-title":"The Natural Function of the Malaria Parasite\u2019s Chloroquine Resistance Transporter","volume":"11","author":"Shafik","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_125","doi-asserted-by":"crossref","unstructured":"Lewis, I.A., Wacker, M., Olszewski, K.L., Cobbold, S.A., Baska, K.S., Tan, A., Ferdig, M.T., and Llin\u00e1s, M. (2014). Metabolic QTL Analysis Links Chloroquine Resistance in Plasmodium Falciparum to Impaired Hemoglobin Catabolism. PLoS Genet., 10.","DOI":"10.1371\/journal.pgen.1004085"},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"683","DOI":"10.1089\/ars.2012.4625","article-title":"Glutathione Transport: A New Role for PfCRT in Chloroquine Resistance","volume":"19","author":"Patzewitz","year":"2013","journal-title":"Antioxid. Redox Signal."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"e01188-14","DOI":"10.1128\/mBio.01188-14","article-title":"Toxoplasma gondii Ingests and Digests Host Cytosolic Proteins","volume":"5","author":"Dou","year":"2014","journal-title":"mBio"},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"17096","DOI":"10.1038\/nmicrobiol.2017.96","article-title":"Toxoplasma Depends on Lysosomal Consumption of Autophagosomes for Persistent Infection","volume":"2","author":"Dou","year":"2017","journal-title":"Nat. Microbiol."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"e00869-19","DOI":"10.1128\/mSphere.00869-19","article-title":"Toxoplasma Cathepsin Protease B and Aspartyl Protease 1 Are Dispensable for Endolysosomal Protein Digestion","volume":"5","author":"McDonald","year":"2020","journal-title":"mSphere"},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"e59384","DOI":"10.7554\/eLife.59384","article-title":"Toxoplasma TgATG9 Is Critical for Autophagy and Long-Term Persistence in Tissue Cysts","volume":"10","author":"Smith","year":"2021","journal-title":"eLife"},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"1119","DOI":"10.1017\/S003118201800001X","article-title":"New and Emerging Uses of CRISPR\/Cas9 to Genetically Manipulate Apicomplexan Parasites","volume":"145","author":"Carruthers","year":"2018","journal-title":"Parasitology"}],"container-title":["Microorganisms"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-2607\/9\/12\/2592\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T07:49:02Z","timestamp":1760168942000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-2607\/9\/12\/2592"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,12,15]]},"references-count":131,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2021,12]]}},"alternative-id":["microorganisms9122592"],"URL":"https:\/\/doi.org\/10.3390\/microorganisms9122592","relation":{},"ISSN":["2076-2607"],"issn-type":[{"value":"2076-2607","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,12,15]]}}}