1887

Abstract

The acquisition and storage of metals has been a preoccupation of life for millennia. Transition metals, in particular iron, copper and zinc, have vital roles within cells. However, metals also make dangerous cargos; inappropriate uptake or storage of transition metals leads to cell death. This paradox has led to cells developing elegant and frequently redundant mechanisms for fine-tuning local metal concentrations. In the context of infection, pathogens must overcome further hurdles, as hosts act to weaponize metal availability to prevent pathogen colonization and spread. Here, we detail the methods used by the Apicomplexa, a large family of eukaryotic parasites, to obtain and store essential metals.

Funding
This study was supported by the:
  • Carnegie Dunfermline Trust (Award RIG009880)
    • Principle Award Recipient: ClareR Harding
  • Wellcome Trust (Award 213455/Z/18/Z)
    • Principle Award Recipient: ClareR Harding
Loading

Article metrics loading...

/content/journal/micro/10.1099/mic.0.001114
2021-12-13
2022-01-28
Loading full text...

Full text loading...

References

  1. Harding CR, Frischknecht F. The riveting cellular structures of apicomplexan parasites. Trends Parasitol 2020; 36:979–991 [View Article] [PubMed]
    [Google Scholar]
  2. Jacot D, Waller RF, Soldati-Favre D, MacPherson DA, MacRae JI. Apicomplexan energy metabolism: carbon source promiscuity and the quiescence hyperbole. Trends Parasitol 2016; 32:56–70 [View Article] [PubMed]
    [Google Scholar]
  3. Striepen B, Jordan CN, Reiff S, van Dooren GG. Building the perfect parasite: cell division in apicomplexa. PLoS Pathog 2007; 3:e78 [View Article] [PubMed]
    [Google Scholar]
  4. Aly ASI, Vaughan AM, Kappe SHI. Malaria parasite development in the mosquito and infection of the mammalian host. Annu Rev Microbiol 2009; 63:195–221 [View Article]
    [Google Scholar]
  5. Venugopal K, Hentzschel F, Valkiūnas G, Marti M. Plasmodium asexual growth and sexual development in the haematopoietic niche of the host. Nat Rev Microbiol 2020; 18:177–189 [View Article]
    [Google Scholar]
  6. Martorelli Di Genova B, Knoll LJ. Comparisons of the sexual cycles for the coccidian parasites Eimeria and Toxoplasma. Front Cell Infect Microbiol 2020; 10:604897 [View Article]
    [Google Scholar]
  7. Tandel J, English ED, Sateriale A, Gullicksrud JA, Beiting DP et al. Life cycle progression and sexual development of the apicomplexan parasite Cryptosporidium parvum. Nat Microbiol 2019; 4:2226–2236 [View Article]
    [Google Scholar]
  8. Kloehn J, Harding CR, Soldati‐Favre D. Supply and demand—heme synthesis, salvage and utilization by Apicomplexa. FEBS J 2020; 288:382–404 [View Article]
    [Google Scholar]
  9. Dellibovi-Ragheb TA, Gisselberg JE, Prigge ST. Parasites FeS Up: Iron-sulfur cluster biogenesis in eukaryotic pathogens. PLoS Pathog 2013; 9:e1003227 [View Article] [PubMed]
    [Google Scholar]
  10. LaGier MJ, Tachezy J, Stejskal F, Kutisova K, Keithly JS. Mitochondrial-type iron-sulfur cluster biosynthesis genes (IscS and IscU) in the apicomplexan Cryptosporidium parvum. Microbiology (Reading) 2003; 149:3519–3530 [View Article] [PubMed]
    [Google Scholar]
  11. Yamasaki S, Shoji M, Kayanuma M, Sladek V, Inaoka DK et al. Weak O2 binding and strong H2O2 binding at the non-heme diiron center of trypanosome alternative oxidase. Biochimica et Biophysica Acta (BBA) - Bioenergetics 2021; 1862:148356 [View Article]
    [Google Scholar]
  12. Goma J, Rénia L, Miltgen F, Mazier D. Iron overload increases hepatic development of Plasmodium yoelii in mice. Parasitology 1996; 112 (Pt 2):165–168 [View Article] [PubMed]
    [Google Scholar]
  13. Muriuki JM, Mentzer AJ, Kimita W, Ndungu FM, Macharia AW et al. Iron status and associated malaria risk among African Children. Clin Infect Dis 2019; 68:1807–1814 [View Article] [PubMed]
    [Google Scholar]
  14. Ferrer P, Tripathi AK, Clark MA, Hand CC, Rienhoff HY et al. Antimalarial iron chelator, FBS0701, shows asexual and gametocyte Plasmodium falciparum activity and single oral dose cure in a murine malaria model. PLoS One 2012; 7:e37171 [View Article]
    [Google Scholar]
  15. Pollack S, Rossan RN, Davidson DE, Escajadillo A. Desferrioxamine suppresses Plasmodium falciparum in Aotus monkeys. Proc Soc Exp Biol Med 1987; 184:162–164 [View Article] [PubMed]
    [Google Scholar]
  16. Thipubon P, Uthaipibull C, Kamchonwongpaisan S, Tipsuwan W, Srichairatanakool S. Inhibitory effect of novel iron chelator, 1-(N-acetyl-6-aminohexyl)-3-hydroxy-2-methylpyridin-4-one (CM1) and green tea extract on growth of Plasmodium falciparum. Malar J 2015; 14:382. [View Article] [PubMed]
    [Google Scholar]
  17. Bunnag D, Poltera AA, Viravan C, Looareesuwan S, Harinasuta KT et al. Plasmodicidal effect of desferrioxamine B in human vivax or falciparum malaria from Thailand. Acta Trop 1992; 52:59–67 [View Article] [PubMed]
    [Google Scholar]
  18. Gordeuk V, Thuma P, Brittenham G, McLaren C, Parry D et al. Effect of iron chelation therapy on recovery from deep coma in children with cerebral malaria. N Engl J Med 1992; 327:1473–1477 [View Article] [PubMed]
    [Google Scholar]
  19. Portugal S, Carret C, Recker M, Armitage AE, Gonçalves LA et al. Host-mediated regulation of superinfection in malaria. Nat Med 2011; 17:732–737 [View Article] [PubMed]
    [Google Scholar]
  20. Thuma PE, Olivieri NF, Mabeza GF, Biemba G, Parry D et al. Assessment of the effect of the oral iron chelator deferiprone on asymptomatic Plasmodium falciparum parasitemia in humans. Am J Trop Med Hyg 1998; 58:358–364 [View Article] [PubMed]
    [Google Scholar]
  21. Maya-Maldonado K, Cardoso-Jaime V, González-Olvera G, Osorio B, Recio-Tótoro B et al. Mosquito metallomics reveal copper and iron as critical factors for Plasmodium infection. PLoS Negl Trop Dis 2021; 15:e0009509. [View Article] [PubMed]
    [Google Scholar]
  22. Almeida MPO, Ferro EAV, Briceño MPP, Oliveira MC, Barbosa BF et al. Susceptibility of human villous (BeWo) and extravillous (HTR-8/SVneo) trophoblast cells to Toxoplasma gondii infection is modulated by intracellular iron availability. Parasitol Res 2019; 118:1559–1572 [View Article] [PubMed]
    [Google Scholar]
  23. Dimier IH, Bout DT. Interferon-gamma-activated primary enterocytes inhibit Toxoplasma gondii replication: a role for intracellular iron. Immunology 1998; 94:488–495 [View Article] [PubMed]
    [Google Scholar]
  24. Mahmoud MS. Effect of deferoxamine alone and combined with pyrimethamine on acute toxoplasmosis in mice. J Egypt Soc Parasitol 1999; 29:791–803 [PubMed]
    [Google Scholar]
  25. Oliveira MC, Coutinho LB, Almeida MPO, Briceño MP, Araujo ECB et al. The availability of iron is involved in the murine experimental Toxoplasma gondii infection outcome. Microorganisms 2020; 8:E560. [View Article] [PubMed]
    [Google Scholar]
  26. Mengist HM, Taye B, Tsegaye A. Intestinal Parasitosis in Relation to CD4+T Cells Levels and Anemia among HAART Initiated and HAART Naive Pediatric HIV Patients in a Model ART Center in Addis Ababa, Ethiopia. PLoS One 2015; 10:e0117715 [View Article] [PubMed]
    [Google Scholar]
  27. Miller CN, Jossé L, Tsaousis AD. Localization of Fe-S biosynthesis machinery in Cryptosporidium parvum mitosome. J Eukaryot Microbiol 2018; 65:913–922 [View Article] [PubMed]
    [Google Scholar]
  28. Clark MA, Goheen MM, Fulford A, Prentice AM, Elnagheeb MA et al. Host iron status and iron supplementation mediate susceptibility to erythrocytic stage Plasmodium falciparum. Nat Commun 2014; 5:4446. [View Article] [PubMed]
    [Google Scholar]
  29. Sigala PA, Crowley JR, Hsieh S, Henderson JP, Goldberg DE. Direct tests of enzymatic heme degradation by the malaria parasite Plasmodium falciparum. J Biol Chem 2012; 287:37793–37807 [View Article] [PubMed]
    [Google Scholar]
  30. Liu J, Istvan ES, Gluzman IY, Gross J, Goldberg DE. Plasmodium falciparum ensures its amino acid supply with multiple acquisition pathways and redundant proteolytic enzyme systems. Proc Natl Acad Sci U S A 2006; 103:8840–8845 [View Article] [PubMed]
    [Google Scholar]
  31. Nagaraj VA, Sundaram B, Varadarajan NM, Subramani PA, Kalappa DM et al. Malaria parasite-synthesized heme is essential in the mosquito and liver stages and complements host heme in the blood stages of infection. PLoS Pathog 2013; 9:e1003522 [View Article]
    [Google Scholar]
  32. Dou Z, McGovern OL, Di Cristina M, Carruthers VB. Toxoplasma gondii ingests and digests host cytosolic proteins. mBio 2014; 5:e01188-14. [View Article] [PubMed]
    [Google Scholar]
  33. Bergmann A, Floyd K, Key M, Dameron C, Rees KC et al. Toxoplasma gondii requires its plant-like heme biosynthesis pathway for infection. PLoS Pathog 2020; 16:e1008499 [View Article] [PubMed]
    [Google Scholar]
  34. Andrews Simon C, Robinson Andrea K. Rodríguez-quiñones francisco. Bacterial Iron Homeostasis 2003; 27:215–237
    [Google Scholar]
  35. Arosio P, Elia L, Poli M. Ferritin, cellular iron storage and regulation. IUBMB Life 2017; 69:414–422 [View Article]
    [Google Scholar]
  36. Zaidi A, Pratap Singh K, Ali V. Leishmania and its quest for iron. Mol Biochem Parasitol 2017; 211:15–25
    [Google Scholar]
  37. Zhang X, Zhang D, Sun W, Wang T. The adaptive mechanism of plants to iron deficiency via iron uptake, transport, and homeostasis. Int J Mol Sci 2019; 20:2424 [View Article]
    [Google Scholar]
  38. Garten M, Nasamu AS, Niles JC, Zimmerberg J, Goldberg DE et al. EXP2 is a nutrient-permeable channel in the vacuolar membrane of Plasmodium and is essential for protein export via PTEX. Nat Microbiol 2018; 3:1090–1098 [View Article] [PubMed]
    [Google Scholar]
  39. Gold DA, Kaplan AD, Lis A, Bett GCL, Rosowski EE et al. The Toxoplasma dense granule proteins GRA17 and GRA23 mediate the movement of small molecules between the host and the parasitophorous vacuole. Cell Host Microbe 2015; 17:642–652 [View Article] [PubMed]
    [Google Scholar]
  40. Sahu T, Boisson B, Lacroix C, Bischoff E, Richier Q et al. ZIPCO, a putative metal ion transporter, is crucial for Plasmodium liver-stage development. EMBO Mol Med 2014; 6:1387–1397 [View Article] [PubMed]
    [Google Scholar]
  41. Ballesteros C, Geary JF, Mackenzie CD, Geary TG. Characterization of Divalent Metal Transporter 1 (DMT1) in Brugia malayi suggests an intestinal-associated pathway for iron absorption. Int J Parasitol Drugs Drug Resist 2018; 8:341–349 [View Article] [PubMed]
    [Google Scholar]
  42. Smyth DJ, Glanfield A, McManus DP, Hacker E, Blair D et al. Two Isoforms of a Divalent Metal Transporter (DMT1) in Schistosoma mansoni suggest a surface-associated pathway for iron absorption in schistosomes. J Biol Chem 2006; 281:2242–2248 [View Article] [PubMed]
    [Google Scholar]
  43. Zaidi A, Singh KP, Ali V. Leishmania and its quest for iron: an update and overview. Mol Biochem Parasitol 2017; 211:15–25 [View Article]
    [Google Scholar]
  44. Dixon SJ, Stockwell BR. The role of iron and reactive oxygen species in cell death. Nat Chem Biol 2014; 10:9–17 [View Article] [PubMed]
    [Google Scholar]
  45. Kim SA, Punshon T, Lanzirotti A, Li L, Alonso JM et al. Localization of iron in Arabidopsis seed requires the vacuolar membrane transporter VIT1. Science 2006; 314:1295–1298 [View Article] [PubMed]
    [Google Scholar]
  46. Li L, Chen OS, McVey Ward D, Kaplan J. CCC1 is a transporter that mediates vacuolar iron storage in yeast. J Biol Chem 2001; 276:29515–29519 [View Article] [PubMed]
    [Google Scholar]
  47. Roschzttardtz H, Conéjéro G, Curie C, Mari S. Identification of the endodermal vacuole as the iron storage compartment in the arabidopsis embryo. Plant Physiol 2009; 151:1329–1338 [View Article] [PubMed]
    [Google Scholar]
  48. Sorribes-Dauden R, Peris D, Martínez-Pastor MT, Puig S. Structure and function of the vacuolar Ccc1/VIT1 family of iron transporters and its regulation in fungi. Comput Struct Biotechnol J 2020; 18:3712–3722 [View Article] [PubMed]
    [Google Scholar]
  49. Zhang Y, Xu Y-H, Yi H-Y, Gong J-M. Vacuolar membrane transporters OsVIT1 and OsVIT2 modulate iron translocation between flag leaves and seeds in rice. Plant J 2012; 72:400–410 [View Article] [PubMed]
    [Google Scholar]
  50. Kato T, Kumazaki K, Wada M, Taniguchi R, Nakane T et al. Crystal structure of plant vacuolar iron transporter VIT1. Nat Plants 2019; 5:308–315 [View Article] [PubMed]
    [Google Scholar]
  51. Labarbuta P, Duckett K, Botting CH, Chahrour O, Malone J et al. Recombinant vacuolar iron transporter family homologue PfVIT from human malaria-causing Plasmodium falciparum is a Fe2+/H+exchanger. Sci Rep 2017; 7:42850 [View Article] [PubMed]
    [Google Scholar]
  52. Sharma P, Tóth V, Hyland EM, Law CJ. Characterization of the substrate binding site of an iron detoxifying membrane transporter from Plasmodium falciparum. Malar J 2021; 20:295. [View Article] [PubMed]
    [Google Scholar]
  53. Slavic K, Krishna S, Lahree A, Bouyer G, Hanson KK et al. A vacuolar iron-transporter homologue acts as a detoxifier in Plasmodium. Nat Commun 2016; 7:10403 [View Article] [PubMed]
    [Google Scholar]
  54. Aghabi D, Sloan M, Dou Z, Guerra AJ, Harding CR. The vacuolar iron transporter mediates iron detoxification in Toxoplasma gondii. bioRXiV 2021
    [Google Scholar]
  55. Nevo Y, Nelson N. The NRAMP family of metal-ion transporters. Biochim Biophys Acta 2006; 1763:609–620 [View Article]
    [Google Scholar]
  56. Sidik SM, Huet D, Ganesan SM, Huynh M-H, Wang T et al. A genome-wide CRISPR screen in toxoplasma identifies essential apicomplexan genes. Cell 2016; 166:1423–1435 [View Article] [PubMed]
    [Google Scholar]
  57. Seo PJ, Park J, Park M-J, Kim Y-S, Kim S-G et al. A Golgi-localized MATE transporter mediates iron homoeostasis under osmotic stress in Arabidopsis. Biochem J 2012; 442:551–561 [View Article] [PubMed]
    [Google Scholar]
  58. Xiao G, Wan Z, Fan Q, Tang X, Zhou B. The metal transporter ZIP13 supplies iron into the secretory pathway in Drosophila melanogaster. eLife 2014; 3:e03191 [View Article] [PubMed]
    [Google Scholar]
  59. Charan M, Choudhary HH, Singh N, Sadik M, Siddiqi MI et al. Fe-S] cluster assembly in the apicoplast and its indispensability in mosquito stages of the malaria parasite. FEBS J 2017; 284:2629–2648 [View Article] [PubMed]
    [Google Scholar]
  60. Gisselberg JE, Dellibovi-Ragheb TA, Matthews KA, Bosch G, Prigge ST. The suf iron-sulfur cluster synthesis pathway is required for apicoplast maintenance in malaria parasites. PLoS Pathog 2013; 9:e1003655 [View Article] [PubMed]
    [Google Scholar]
  61. Wang J, Pantopoulos K. Regulation of cellular iron metabolism. Biochem J 2011; 434:365–381 [View Article] [PubMed]
    [Google Scholar]
  62. Alén C, Sonenshein AL. Bacillus subtilis aconitase is an RNA-binding protein. Proc Natl Acad Sci U S A 1999; 96:10412–10417 [View Article] [PubMed]
    [Google Scholar]
  63. Marondedze C, Thomas L, Serrano NL, Lilley KS, Gehring C. The RNA-binding protein repertoire of Arabidopsis thaliana. Sci Rep 2016; 6:29766. [View Article] [PubMed]
    [Google Scholar]
  64. Tang Y, Guest JR. Direct evidence for mRNA binding and post-transcriptional regulation by Escherichia coli aconitases. Microbiology (Reading) 1999; 145 (Pt 11):3069–3079 [View Article] [PubMed]
    [Google Scholar]
  65. Hentze MW, Rouault TA, Caughman SW, Dancis A, Harford JB et al. A cis-acting element is necessary and sufficient for translational regulation of human ferritin expression in response to iron. Proc Natl Acad Sci U S A 1987; 84:6730–6734 [View Article] [PubMed]
    [Google Scholar]
  66. Koeller DM, Casey JL, Hentze MW, Gerhardt EM, Chan LN et al. A cytosolic protein binds to structural elements within the iron regulatory region of the transferrin receptor mRNA. Proc Natl Acad Sci U S A 1989; 86:3574–3578 [View Article] [PubMed]
    [Google Scholar]
  67. Loyevsky M, LaVaute T, Allerson CR, Stearman R, Kassim OO et al. An IRP-like protein from Plasmodium falciparum binds to a mammalian iron-responsive element. Blood 2001; 98:2555–2562 [View Article] [PubMed]
    [Google Scholar]
  68. Hodges M, Yikilmaz E, Patterson G, Kasvosve I, Rouault TA et al. An iron regulatory-like protein expressed in Plasmodium falciparum displays aconitase activity. Mol Biochem Parasitol 2005; 143:29–38 [View Article] [PubMed]
    [Google Scholar]
  69. Loyevsky M, Mompoint F, Yikilmaz E, Altschul SF, Madden T et al. Expression of a recombinant IRP-like Plasmodium falciparum protein that specifically binds putative plasmodial IREs. Mol Biochem Parasitol 2003; 126:231–238 [View Article] [PubMed]
    [Google Scholar]
  70. Gail M, Gross U, Bohne W. Transferrin receptor induction in Toxoplasma gondii-infected HFF is associated with increased iron-responsive protein 1 activity and is mediated by secreted factors. Parasitol Res 2004; 94:233–239 [View Article]
    [Google Scholar]
  71. Hakimi M-A, Olias P, Sibley LD. Toxoplasma effectors targeting host signaling and transcription. Clin Microbiol Rev 2017; 30:615–645 [View Article]
    [Google Scholar]
  72. Cassandri M, Smirnov A, Novelli F, Pitolli C, Agostini M et al. Zinc-finger proteins in health and disease. Cell Death Discov 2017; 3:17071 [View Article] [PubMed]
    [Google Scholar]
  73. Eide DJ. Zinc transporters and the cellular trafficking of zinc. Biochimica et Biophysica Acta (BBA) - Molecular Cell Research. Cell Biology of Metals 1763711–722
    [Google Scholar]
  74. Gopalakrishnan AM, Aly ASI, Aravind L, Kumar N. Multifunctional Involvement of a C2H2 Zinc Finger Protein (PbZfp) in malaria transmission, histone modification, and susceptibility to DNA damage response. mBio 2017; 8:e01298-17. [View Article] [PubMed]
    [Google Scholar]
  75. Hajagos BE, Turetzky JM, Peng ED, Cheng SJ, Ryan CM et al. Molecular dissection of novel trafficking and processing of the Toxoplasma gondii rhoptry metalloprotease toxolysin-1. Traffic 2012; 13:292–304 [View Article] [PubMed]
    [Google Scholar]
  76. Semenovskaya K, Lévêque MF, Berry L, Bordat Y, Dubremetz J-F et al. TgZFP2 is a novel zinc finger protein involved in coordinating mitosis and budding in Toxoplasma. Cell Microbiol 2020; 22:e13120 [View Article] [PubMed]
    [Google Scholar]
  77. Tanveer A, Allen SM, Jackson KE, Charan M, Ralph SA et al. An FtsH protease is recruited to the mitochondrion of Plasmodium falciparum. PLOS ONE 2013; 8:e74408 [View Article] [PubMed]
    [Google Scholar]
  78. Marvin RG, Wolford JL, Kidd MJ, Murphy S, Ward J et al. Fluxes in “free” and total zinc are essential for progression of intraerythrocytic stages of Plasmodium falciparum. Chem Biol 2012; 19:731–741 [View Article] [PubMed]
    [Google Scholar]
  79. Al-Sandaqchi AT, Brignell C, Collingwood JF, Geraki K, Mirkes EM et al. Metallome of cerebrovascular endothelial cells infected with Toxoplasma gondii using μ-XRF imaging and inductively coupled plasma mass spectrometry. Metallomics 2018; 10:1401–1414 [View Article] [PubMed]
    [Google Scholar]
  80. Kumari A, Singh KP, Mandal A, Paswan RK, Sinha P et al. Intracellular zinc flux causes reactive oxygen species mediated mitochondrial dysfunction leading to cell death in Leishmania donovani. PLoS ONE 2017; 12:e0178800 [View Article]
    [Google Scholar]
  81. Hamaguchi K. Nippon V. and L.S.U., Takahashi, J., Suzuki, C., Honma, H., Nakai, Y., Imai, S Infectivity of Cryptosporidium muris and C. parvum to zinc deficient rats and mice. Bulletin of the Nippon Veterinary and Life Science University 2006
    [Google Scholar]
  82. Müller O, Becher H, van Zweeden AB, Ye Y, Diallo DA et al. Effect of zinc supplementation on malaria and other causes of morbidity in west African children: randomised double blind placebo controlled trial. BMJ 2001; 322:1567 [View Article] [PubMed]
    [Google Scholar]
  83. Veenemans J, Milligan P, Prentice AM, Schouten LRA, Inja N et al. Effect of supplementation with zinc and other micronutrients on malaria in tanzanian children: a randomised trial. PLoS Med 2011; 8:e1001125 [View Article] [PubMed]
    [Google Scholar]
  84. Subramanian Vignesh K, Deepe GS. Immunological orchestration of zinc homeostasis: the battle between host mechanisms and pathogen defenses. Arch Biochem Biophys 2016; 611:66–78 [View Article] [PubMed]
    [Google Scholar]
  85. Maret W. Molecular aspects of human cellular zinc homeostasis: redox control of zinc potentials and zinc signals. Biometals 2009; 22:149–157 [View Article] [PubMed]
    [Google Scholar]
  86. Maret W, Krezel A. Cellular zinc and redox buffering capacity of metallothionein/thionein in health and disease. Mol Med 2007; 13:371–375 [View Article] [PubMed]
    [Google Scholar]
  87. Plum LM, Rink L, Haase H. The essential toxin: impact of zinc on human health. Int J Environ Res Public Health 2010; 7:1342–1365 [View Article] [PubMed]
    [Google Scholar]
  88. Chasen NM, Stasic AJ, Asady B, Coppens I, Moreno SNJ et al. The Vacuolar Zinc Transporter TgZnT Protects Toxoplasma gondii from Zinc Toxicity. mSphere 2019; 4: [View Article]
    [Google Scholar]
  89. Luo S, Vieira M, Graves J, Zhong L, Moreno SN. A plasma membrane-type Ca(2+)-ATPase co-localizes with a vacuolar H(+)-pyrophosphatase to acidocalcisomes of Toxoplasma gondii. EMBO J 2001; 20:55–64 [View Article] [PubMed]
    [Google Scholar]
  90. Rohloff P, Miranda K, Rodrigues JCF, Fang J, Galizzi M et al. Calcium uptake and proton transport by acidocalcisomes of Toxoplasma gondii. PLOS ONE 2011; 6:e18390 [View Article] [PubMed]
    [Google Scholar]
  91. Aurrecoechea C, Brestelli J, Brunk BP, Dommer J, Fischer S et al. PlasmoDB: a functional genomic database for malaria parasites. Nucleic Acids Res 2009; 37:D539–43 [View Article] [PubMed]
    [Google Scholar]
  92. Kenthirapalan S, Waters AP, Matuschewski K, Kooij TWA. Functional profiles of orphan membrane transporters in the life cycle of the malaria parasite. Nat Commun 2016; 7:10519 [View Article] [PubMed]
    [Google Scholar]
  93. Sayers CP, Mollard V, Buchanan HD, McFadden GI, Goodman CD. A genetic screen in rodent malaria parasites identifies five new apicoplast putative membrane transporters, one of which is essential in human malaria parasites. Cell Microbiol 2018; 20:e12789 [View Article] [PubMed]
    [Google Scholar]
  94. Bafaro E, Liu Y, Xu Y, Dempski RE. The emerging role of zinc transporters in cellular homeostasis and cancer. Signal Transduct Target Ther 2017; 2:17029. [View Article] [PubMed]
    [Google Scholar]
  95. Balamurugan K, Schaffner W. Copper homeostasis in eukaryotes: Teetering on a tightrope. Biochimica et Biophysica Acta (BBA) - Molecular Cell Research. Cell Biology of Metals 2006; 1763:737–746
    [Google Scholar]
  96. Asahi H, Tolba MEM, Tanabe M, Sugano S, Abe K et al. Perturbation of copper homeostasis is instrumental in early developmental arrest of intraerythrocytic Plasmodium falciparum. BMC Microbiol 2014; 14:167. [View Article] [PubMed]
    [Google Scholar]
  97. Rasoloson D, Shi L, Chong CR, Kafsack BF, Sullivan DJ. Copper pathways in Plasmodium falciparum infected erythrocytes indicate an efflux role for the copper P-ATPase. Biochem J 2004; 381:803–811 [View Article] [PubMed]
    [Google Scholar]
  98. Liu S, Roellig DM, Guo Y, Li N, Frace MA et al. Evolution of mitosome metabolism and invasion-related proteins in Cryptosporidium. BMC Genomics 2016; 17:1006 [View Article]
    [Google Scholar]
  99. LaGier MJ, Zhu G, Keithly JS. Characterization of a heavy metal ATPase from the apicomplexan Cryptosporidium parvum. Gene 2001; 266:25–34 [View Article]
    [Google Scholar]
  100. Li C, Li Y, Ding C. The role of copper homeostasis at the host-pathogen axis: from bacteria to fungi. IJMS 2019; 20:175 [View Article]
    [Google Scholar]
  101. Kaplan JH, Maryon EB. How mammalian cells acquire copper: an essential but potentially toxic metal. Biophys J 2016; 110:7–13 [View Article] [PubMed]
    [Google Scholar]
  102. Choveaux DL, Przyborski JM, Goldring JPD. A Plasmodium falciparum copper-binding membrane protein with copper transport motifs. Malar J 2012; 11:397. [View Article] [PubMed]
    [Google Scholar]
  103. Kenthirapalan S, Waters AP, Matuschewski K, Kooij TWA. Copper-transporting ATPase is important for malaria parasite fertility. Mol Microbiol 2014; 91:315–325 [View Article] [PubMed]
    [Google Scholar]
  104. Zhu X, Boulet A, Buckley KM, Phillips CB, Gammon MG et al. Mitochondrial copper and phosphate transporter specificity was defined early in the evolution of eukaryotes. eLife 2021; 10:e64690 [View Article]
    [Google Scholar]
  105. Blaby-Haas CE, Merchant SS. The ins and outs of algal metal transport. Biochim Biophys Acta 2012; 1823:1531–1552 [View Article]
    [Google Scholar]
  106. Ehrensberger KM, Bird AJ. Hammering out details: regulating metal levels in eukaryotes. Trends Biochem Sci 2011; 36:524–531 [View Article]
    [Google Scholar]
  107. Zhang M, Wang C, Otto TD, Oberstaller J, Liao X et al. Uncovering the essential genes of the human malaria parasite Plasmodium falciparum by saturation mutagenesis. Science 2018; 360:eaap7847. [View Article] [PubMed]
    [Google Scholar]
  108. Barylyuk K, Koreny L, Ke H, Butterworth S, Crook OM et al. A comprehensive subcellular atlas of the toxoplasma proteome via hyperLOPIT provides spatial context for protein functions. Cell Host & Microbe 2020; 28:752–766 [View Article]
    [Google Scholar]
  109. Choveaux DL, Krause RGE, Przyborski JM, Goldring JPD. Identification and initial characterisation of a Plasmodium falciparum Cox17 copper metallochaperone. Exp Parasitol 2015; 148:30–39 [View Article] [PubMed]
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/micro/10.1099/mic.0.001114
Loading
/content/journal/micro/10.1099/mic.0.001114
Loading

Data & Media loading...

Most cited this month Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error