Membrane transport in the malaria parasite and its host erythrocyte

Biochemical Journal

Volumn 457, Issue 1, 2014, Pages 1-18

  Kirk, Kiaran ^a   Lehane, Adele M ^a  

^a AUSTRALIAN NATIONAL UNIVERSITY   (Australia)

Author keywords

Channel; Ion homoeostasis; Metabolite; Nutrient uptake; Plasmodium falciparum; Transporter

Indexed keywords

4 AMINOBENZOIC ACID; ANTIMALARIAL AGENT; ANTINEOPLASTIC AGENT; AQUAGLYCEROPORIN; ARTEMISININ; ARTEMISININ DERIVATIVE; BENFLUMETOL; BLASTICIDIN S; CALCIUM; CHLOROQUINE; FOLIC ACID; FOSMIDOMYCIN; GLUTATHIONE; HALOFANTRINE; ISOLEUCINE; LEUPEPTIN; MEFLOQUINE; METHIONINE; MONOSACCHARIDE; MULTIDRUG RESISTANCE PROTEIN 1; NUCLEOSIDE; NUCLEOTIDE; PENTAMIDINE; PEPSTATIN; POLYOL; POTASSIUM; PROTON; QUININE; SODIUM;

AMINO ACID TRANSPORT; ANTIMALARIAL DRUG SUSCEPTIBILITY; CELL VACUOLE; CHLORIDE TRANSPORT; DRUG TRANSPORT; ERYTHROCYTE; HOST PARASITE INTERACTION; ION CONDUCTANCE; MALARIA; MEMBRANE PERMEABILITY; MEMBRANE TRANSPORT; MUTATION; NONHUMAN; NUCLEOTIDE TRANSPORT; OXIDATIVE STRESS; PLASMODIUM; PLASMODIUM BERGHEI; PLASMODIUM FALCIPARUM; POTASSIUM TRANSPORT; PRIORITY JOURNAL; PROTON TRANSPORT; REVIEW; SODIUM TRANSPORT;

ANIMALS; BIOLOGICAL TRANSPORT; ERYTHROCYTE MEMBRANE; ERYTHROCYTES; HOST-PARASITE INTERACTIONS; HUMANS; MALARIA; MEMBRANE TRANSPORT PROTEINS; PLASMODIUM FALCIPARUM;

EID: 84890054516     PISSN: 02646021     EISSN: 14708728     Source Type: Journal    
DOI: 10.1042/BJ20131007     Document Type: Review

References (222)

1. Ginsburg, H., Kutner, S., Krugliak, M. and Cabantchik, Z. I. (1985) Characterization of permeation pathways appearing in the host membrane of Plasmodium falciparum infected red blood cells. Mol. Biochem. Parasitol. 14, 313-322
2. Kirk, K., Horner, H. A., Elford, B. C., Ellory, J. C. and Newbold, C. I. (1994) Transport of diverse substrates into malaria-infected erythrocytes via a pathway showing functional characteristics of a chloride channel. J. Biol. Chem. 269, 3339-3347
3. Ginsburg, H. and Stein, W. D. (2004) The new permeability pathways induced by the malaria parasite in the membrane of the infected erythrocyte: comparison of results using different experimental techniques. J. Membr. Biol. 197, 113-134
4. Lisk, G., Scott, S., Solomon, T., Pillai, A. D. and Desai, S. A. (2007) Solute-inhibitor interactions in the plasmodial surface anion channel reveal complexities in the transport process. Mol. Pharmacol. 71, 1241-1250
5. Staines, H. M., Rae, C. and Kirk, K. (2000) Increased permeability of the malaria-infected erythrocyte to organic cations. Biochim. Biophys. Acta 1463, 88-98
6. Staines, H. M., Alkhalil, A., Allen, R. J., De Jonge, H. R., Derbyshire, E., Egee, S., Ginsburg, H., Hill, D. A., Huber, S. M., Kirk, K. et al. (2007) Electrophysiological studies of malaria parasite-infected erythrocytes: current status. Int. J. Parasitol. 37, 475-482
7. - channels of human erythrocytes by membrane oxidation. EMBO J. 21, 22-30
8. Egee, S., Lapaix, F., Decherf, G., Staines, H. M., Ellory, J. C., Doerig, C. and Thomas, S. L. (2002) A stretch-activated anion channel is up-regulated by the malaria parasite Plasmodium falciparum. J. Physiol. 542, 795-801
9. Merckx, A., Bouyer, G., Thomas, S. L., Langsley, G. and Egee, S. (2009) Anion channels in Plasmodium-falciparum-infected erythrocytes and protein kinase A. Trends Parasitol. 25, 139-144
10. Merckx, A., Nivez, M. P., Bouyer, G., Alano, P., Langsley, G., Deitsch, K., Thomas, S., Doerig, C. and Egee, S. (2008) Plasmodium falciparum regulatory subunit of cAMP-dependent PKA and anion channel conductance. PLoS Pathog. 4, e19
11. Staines, H. M., Powell, T., Ellory, J. C., Egee, S., Lapaix, F., Decherf, G., Thomas, S. L., Duranton, C., Lang, F. and Huber, S. M. (2003) Modulation of whole-cell currents in Plasmodium falciparum-infected human red blood cells by holding potential and serum. J. Physiol. 552, 177-183
12. Huber, S. M. (2012) Purinoceptor signaling in malaria-infected erythrocytes. Microbes Infect. 14, 779-786
13. Tanneur, V., Duranton, C., Brand, V. B., Sandu, C. D., Akkaya, C., Kasinathan, R. S., Gachet, C., Sluyter, R., Barden, J. A., Wiley, J. S. et al. (2006) Purinoceptors are involved in the induction of an osmolyte permeability in malaria-infected and oxidized human erythrocytes. FASEB J. 20, 133-135
14. Huber, S. M., Duranton, C., Henke, G., Van De Sand, C., Heussler, V., Shumilina, E., Sandu, C. D., Tanneur, V., Brand, V., Kasinathan, R. S. et al. (2004) Plasmodium induces swelling-activated ClC-2 anion channels in the host erythrocyte. J. Biol. Chem. 279, 41444-41452
15. Verloo, P., Kocken, C. H., Van der Wel, A., Tilly, B. C., Hogema, B. M., Sinaasappel, M., Thomas, A. W. and De Jonge, H. R. (2004) Plasmodium falciparum-activated chloride channels are defective in erythrocytes from cystic fibrosis patients. J. Biol. Chem. 279, 10316-10322
16. Bouyer, G., Cueff, A., Egee, S., Kmiecik, J., Maksimova, Y., Glogowska, E., Gallagher, P. G. and Thomas, S. L. (2011) Erythrocyte peripheral type benzodiazepine receptor/voltage-dependent anion channels are upregulated by Plasmodium falciparum. Blood 118, 2305-2312
17. Winterberg, M., Rajendran, E., Baumeister, S., Bietz, S., Kirk, K. and Lingelbach, K. (2012) Chemical activation of a high-affinity glutamate transporter in human erythrocytes and its implications for malaria-parasite- induced glutamate uptake. Blood 119, 3604-3612
18. Desai, S. A. (2012) Ion and nutrient uptake by malaria parasite-infected erythrocytes. Cell. Microbiol. 14, 1003-1009
19. Nguitragool, W., Bokhari, A. A., Pillai, A. D., Rayavara, K., Sharma, P., Turpin, B., Aravind, L. and Desai, S. A. (2011) Malaria parasite clag3 genes determine channel-mediated nutrient uptake by infected red blood cells. Cell 145, 665-677
20. Mira-Martinez, S., Rovira-Graells, N., Crowley, V. M., Altenhofen, L. M., Llinas, M. and Cortes, A. (2013) Epigenetic switches in clag3 genes mediate blasticidin S resistance in malaria parasites. Cell. Microbiol. 15, 1913-1923
21. Sharma, P., Wollenberg, K., Sellers, M., Zainabadi, K., Galinsky, K., Moss, E., Nguitragool, W., Neafsey, D. and Desai, S. A. (2013) An epigenetic antimalarial resistance mechanism involving parasite genes linked to nutrient uptake. J. Biol. Chem. 288, 19429-19440
22. Ekland, E. H., Akabas, M. H. and Fidock, D. A. (2011) Taking charge: feeding malaria via anion channels. Cell 145, 645-647
23. Divo, A. A., Geary, T. G., Davis, N. L. and Jensen, J. B. (1985) Nutritional requirements of Plasmodium falciparum in culture. I. Exogenously supplied dialyzable components necessary for continuous growth. J. Protozool. 32, 59-64
24. Kirk, K., Horner, H. A. and Kirk, J. (1996) Glucose uptake in Plasmodium falciparum-infected erythrocytes is an equilibrative not an active process. Mol. Biochem. Parasitol. 82, 195-205
25. Quashie, N. B., Ranford-Cartwright, L. C. and de Koning, H. P. (2010) Uptake of purines in Plasmodium falciparum-infected human erythrocytes is mostly mediated by the human equilibrative nucleoside transporter and the human facilitative nucleobase transporter. Malar. J. 9, 36
26. Saliba, K. J., Horner, H. A. and Kirk, K. (1998) Transport and metabolism of the essential vitamin pantothenic acid in human erythrocytes infected with the malaria parasite Plasmodium falciparum. J. Biol. Chem. 273, 10190-10195
27. Spry, C. and Saliba, K. J. (2009) The human malaria parasite Plasmodium falciparum is not dependent on host coenzyme A biosynthesis. J. Biol. Chem. 284, 24904-24913
28. Wagner, C. A., Lang, F. and Broer, S. (2001) Function and structure of heterodimeric amino acid transporters. Am. J. Physiol. Cell Physiol. 281, C1077-C1093
29. Martin, R. E. and Kirk, K. (2007) Transport of the essential nutrient isoleucine in human erythrocytes infected with the malaria parasite Plasmodium falciparum. Blood 109, 2217-2224
30. Cobbold, S. A., Martin, R. E. and Kirk, K. (2011) Methionine transport in the malaria parasite Plasmodium falciparum. Int. J. Parasitol. 41, 125-135
31. Pillai, A. D., Nguitragool, W., Lyko, B., Dolinta, K., Butler, M. M., Nguyen, S. T., Peet, N. P., Bowlin, T. L. and Desai, S. A. (2012) Solute restriction reveals an essential role for clag3-associated channels in malaria parasite nutrient acquisition. Mol. Pharmacol. 82, 1104-1114
32. Poole, R. C. and Halestrap, A. P. (1993) Transport of lactate and other monocarboxylates across mammalian plasma membranes. Am. J. Physiol. 264, C761-C782
33. Krugliak, M., Zhang, J. and Ginsburg, H. (2002) Intraerythrocytic Plasmodium falciparum utilizes only a fraction of the amino acids derived from the digestion of host cell cytosol for the biosynthesis of its proteins. Mol. Biochem. Parasitol. 119, 249-256
34. + exclusion. Mol. Biochem. Parasitol. 132, 27-34
35. + in malaria-infected erythrocytes. Am. J. Physiol. Cell Physiol. 280, C1576-C1587
36. Mauritz, J. M., Esposito, A., Ginsburg, H., Kaminski, C. F., Tiffert, T. and Lew, V. L. (2009) The homeostasis of Plasmodium falciparum-infected red blood cells. PLoS Comput. Biol. 5, e1000339
37. Lee, P., Ye, Z., Van Dyke, K. and Kirk, R. G. (1988) X-ray microanalysis of Plasmodium falciparum and infected red blood cells: effects of qinghaosu and chloroquine on potassium, sodium, and phosphorus composition. Am. J. Trop. Med. Hyg. 39, 157-165
38. Mauritz, J. M., Seear, R., Esposito, A., Kaminski, C. F., Skepper, J. N., Warley, A., Lew, V. L. and Tiffert, T. (2011) X-ray microanalysis investigation of the changes in Na, K, and hemoglobin concentration in Plasmodium falciparum-infected red blood cells. Biophys. J. 100, 1438-1445
39. Pillai, A. D., Addo, R., Sharma, P., Nguitragool, W., Srinivasan, P. and Desai, S. A. (2013) Malaria parasites tolerate a broad range of ionic environments and do not require host cation remodelling. Mol. Microbiol. 88, 20-34
40. Brand, V. B., Sandu, C. D., Duranton, C., Tanneur, V., Lang, K. S., Huber, S. M. and Lang, F. (2003) Dependence of Plasmodium falciparum in vitro growth on the cation permeability of the human host erythrocyte. Cell. Physiol. Biochem. 13, 347-356
41. Desai, S. A., Krogstad, D. J. and McCleskey, E. W. (1993) A nutrient-permeable channel on the intraerythrocytic malaria parasite. Nature 362, 643-646
42. Desai, S. A. and Rosenberg, R. L. (1997) Pore size of the malaria parasite's nutrient channel. Proc. Natl. Acad. Sci. U.S.A. 94, 2045-2049
43. Schwab, J. C., Beckers, C. J. and Joiner, K. A. (1994) The parasitophorous vacuole membrane surrounding intracellular Toxoplasma gondii functions as a molecular sieve. Proc. Natl. Acad. Sci. U.S.A. 91, 509-513
44. Nyalwidhe, J., Baumeister, S., Hibbs, A. R., Tawill, S., Papakrivos, J., Volker, U. and Lingelbach, K. (2002) A nonpermeant biotin derivative gains access to the parasitophorous vacuole in Plasmodium falciparum-infected erythrocytes permeabilized with streptolysin O. J. Biol. Chem. 277, 40005-40011
45. de Koning-Ward, T. F., Gilson, P. R., Boddey, J. A., Rug, M., Smith, B. J., Papenfuss, A. T., Sanders, P. R., Lundie, R. J., Maier, A. G., Cowman, A. F. and Crabb, B. S. (2009) A newly discovered protein export machine in malaria parasites. Nature 459, 945-949
46. Gazarini, M. L., Thomas, A. P., Pozzan, T. and Garcia, C. R. (2003) Calcium signaling in a low calcium environment: how the intracellular malaria parasite solves the problem. J. Cell Biol. 161, 103-110
47. Martin, R. E., Ginsburg, H. and Kirk, K. (2009) Membrane transport proteins of the malaria parasite. Mol. Microbiol. 74, 519-528
48. Martin, R. E., Henry, R. I., Abbey, J. L., Clements, J. D. and Kirk, K. (2005) The 'permeome' of the malaria parasite: An overview of the membrane transport proteins of Plasmodium falciparum. Genome Biol. 6, R26
49. Saliba, K. J., Krishna, S. and Kirk, K. (2004) Inhibition of hexose transport and abrogation of pH homeostasis in the intraerythrocytic malaria parasite by an O-3-hexose derivative. FEBS Lett. 570, 93-96
50. Downie, M. J., Saliba, K. J., Howitt, S. M., Broer, S. and Kirk, K. (2006) Transport of nucleosides across the Plasmodium falciparum parasite plasma membrane has characteristics of PfENT1. Mol. Microbiol. 60, 738-748
51. Downie, M. J., Saliba, K. J., Broer, S., Howitt, S. M. and Kirk, K. (2008) Purine nucleobase transport in the intraerythrocytic malaria parasite. Int. J. Parasitol. 38, 203-209
52. + -coupled pantothenate transport in the intracellular malaria parasite. J. Biol. Chem. 276, 18115-18121
53. Saliba, K. J., Martin, R. E., Broer, A., Henry, R. I., McCarthy, C. S., Downie, M. J., Allen, R. J., Mullin, K. A., McFadden, G. I., Broer, S. and Kirk, K. (2006) Sodium-dependent uptake of inorganic phosphate by the intracellular malaria parasite. Nature 443, 582-585
54. Allen, R. J. and Kirk, K. (2004) The membrane potential of the intraerythrocytic malaria parasite Plasmodium falciparum. J. Biol. Chem. 279, 11264-11272
55. Biagini, G. A., Pasini, E. M., Hughes, R., De Koning, H. P., Vial, H. J., O'Neill, P. M., Ward, S. A. and Bray, P. G. (2004) Characterization of the choline carrier of Plasmodium falciparum: A route for the selective delivery of novel antimalarial drugs. Blood 104, 3372-3377
56. Lehane, A. M., Saliba, K. J., Allen, R. J. and Kirk, K. (2004) Choline uptake into the malaria parasite is energized by the membrane potential. Biochem. Biophys. Res. Commun. 320, 311-317
57. Niemand, J., Louw, A. I., Birkholtz, L. and Kirk, K. (2012) Polyamine uptake by the intraerythrocytic malaria parasite, Plasmodium falciparum. Int. J. Parasitol. 42, 921-929
58. van Dooren, G. G., Stimmler, L. M. and McFadden, G. I. (2006) Metabolic maps and functions of the Plasmodium mitochondrion. FEMS Microbiol. Rev. 30, 596-630
59. Macrae, J. I., Dixon, M. W., Dearnley, M. K., Chua, H. H., Chambers, J. M., Kenny, S., Bottova, I., Tilley, L. and McConville, M. J. (2013) Mitochondrial metabolism of sexual and asexual blood stages of the malaria parasite Plasmodium falciparum. BMC Biol. 11,67
60. Krishna, S., Woodrow, C. J., Burchmore, R. J., Saliba, K. J. and Kirk, K. (2000) Hexose transport in asexual stages of Plasmodium falciparum and kinetoplastidae. Parasitol. Today 16, 516-521
61. Woodrow, C. J., Burchmore, R. J. and Krishna, S. (2000) Hexose permeation pathways in Plasmodium falciparum-infected erythrocytes. Proc. Natl. Acad. Sci. U.S.A. 97, 9931-9936
62. Woodrow, C. J., Penny, J. I. and Krishna, S. (1999) Intraerythrocytic Plasmodium falciparum expresses a high affinity facilitative hexose transporter. J. Biol. Chem. 274, 7272-7277
63. Slavic, K., Straschil, U., Reininger, L., Doerig, C., Morin, C., Tewari, R. and Krishna, S. (2010) Life cycle studies of the hexose transporter of Plasmodium species and genetic validation of their essentiality. Mol. Microbiol. 75, 1402-1413
64. Tjhin, E. T., Staines, H. M., van Schalkwyk, D. A., Krishna, S. and Saliba, K. J. (2013) Studies with the Plasmodium falciparum hexokinase reveal that PfHT limits the rate of glucose entry into glycolysis. FEBS Lett. 587, 3182-3187
65. Blume, M., Hliscs, M., Rodriguez-Contreras, D., Sanchez, M., Landfear, S., Lucius, R., Matuschewski, K. and Gupta, N. (2011) A constitutive pan-hexose permease for the Plasmodium life cycle and transgenic models for screening of antimalarial sugar analogs. FASEB J. 25, 1218-1229
66. Slavic, K., Delves, M. J., Prudencio, M., Talman, A. M., Straschil, U., Derbyshire, E. T., Xu, Z., Sinden, R. E., Mota, M. M., Morin, C. et al. (2011) Use of a selective inhibitor to define the chemotherapeutic potential of the plasmodial hexose transporter in different stages of the parasite's life cycle. Antimicrob. Agents Chemother. 55, 2824-2830
67. Joet, T., Eckstein-Ludwig, U., Morin, C. and Krishna, S. (2003) Validation of the hexose transporter of Plasmodium falciparum as a novel drug target. Proc. Natl. Acad. Sci. U.S.A. 100, 7476-7479
68. Lian, L. Y., Al-Helal, M., Roslaini, A. M., Fisher, N., Bray, P. G., Ward, S. A. and Biagini, G. A. (2009) Glycerol: An unexpected major metabolite of energy metabolism by the human malaria parasite. Malar. J. 8, 38
69. Newby, Z. E., O'Connell, J., Robles-Colmenares, Y., Khademi, S., Miercke, L. J. and Stroud, R. M. (2008) Crystal structure of the aquaglyceroporin PfAQP from the malarial parasite Plasmodium falciparum. Nat. Struct. Mol. Biol. 15, 619-625
70. Liu, Y., Promeneur, D., Rojek, A., Kumar, N., Frokiaer, J., Nielsen, S., King, L. S., Agre, P. and Carbrey, J. M. (2007) Aquaporin 9 is the major pathway for glycerol uptake by mouse erythrocytes, with implications for malarial virulence. Proc. Natl. Acad. Sci. U.S.A. 104, 12560-12564
71. Hansen, M., Kun, J. F., Schultz, J. E. and Beitz, E. (2002) A single, bi-functional aquaglyceroporin in blood-stage Plasmodium falciparum malaria parasites. J. Biol. Chem. 277, 4874-4882
72. Promeneur, D., Liu, Y., Maciel, J., Agre, P., King, L. S. and Kumar, N. (2007) Aquaglyceroporin PbAQP during intraerythrocytic development of the malaria parasite Plasmodium berghei. Proc. Natl. Acad. Sci. U.S.A. 104, 2211-2216
73. Kenthirapalan, S., Waters, A. P., Matuschewski, K. and Kooij, T. W. (2012) Flow cytometry-assisted rapid isolation of recombinant Plasmodium berghei parasites exemplified by functional analysis of aquaglyceroporin. Int. J. Parasitol. 42, 1185-1192
74. Mehta, M., Sonawat, H. M. and Sharma, S. (2005) Malaria parasite-infected erythrocytes inhibit glucose utilization in uninfected red cells. FEBS Lett. 579, 6151-6158
75. Cranmer, S. L., Conant, A. R., Gutteridge, W. E. and Halestrap, A. P. (1995) Characterization of the enhanced transport of L- and D-lactate into human red blood cells infected with Plasmodium falciparum suggests the presence of a novel saturable lactate proton cotransporter. J. Biol. Chem. 270, 15045-15052
76. Elliott, J. L., Saliba, K. J. and Kirk, K. (2001) Transport of lactate and pyruvate in the intraerythrocytic malaria parasite, Plasmodium falciparum. Biochem. J. 355, 733-739
77. Downie, M. J., Kirk, K. and Mamoun, C. B. (2008) Purine salvage pathways in the intraerythrocytic malaria parasite Plasmodium falciparum. Eukaryot. Cell 7, 1231-1237
78. Kirk, K., Howitt, S. M., Broer, S., Saliba, K. J. and Downie, M. J. (2009) Purine uptake in Plasmodium: transport versus metabolism. Trends Parasitol. 25, 246-249
79. Riegelhaupt, P. M., Cassera, M. B., Frohlich, R. F., Hazleton, K. Z., Hefter, J. J., Schramm, V. L. and Akabas, M. H. (2010) Transport of purines and purine salvage pathway inhibitors by the Plasmodium falciparum equilibrative nucleoside transporter PfENT1. Mol. Biochem. Parasitol. 169, 40-49
80. Upston, J. M. and Gero, A. M. (1995) Parasite-induced permeation of nucleosides in Plasmodium falciparum malaria. Biochim. Biophys. Acta 1236, 249-258
81. Carter, N. S., Ben Mamoun, C., Liu, W., Silva, E. O., Landfear, S. M., Goldberg, D. E. and Ullman, B. (2000) Isolation and functional characterization of the PfNT1 nucleoside transporter gene from Plasmodium falciparum. J. Biol. Chem. 275, 10683-10691
82. Parker, M. D., Hyde, R. J., Yao, S. Y., McRobert, L., Cass, C. E., Young, J. D., McConkey, G. A. and Baldwin, S. A. (2000) Identification of a nucleoside/nucleobase transporter rom Plasmodium falciparum, a novel target for anti-malarial chemotherapy. Biochem. J. 349, 67-75
83. Rager, N., Mamoun, C. B., Carter, N. S., Goldberg, D. E. and Ullman, B. (2001) Localization of the Plasmodium falciparum PfNT1 nucleoside transporter to the parasite plasma membrane. J. Biol. Chem. 276, 41095-41099
84. Riegelhaupt, P. M., Frame, I. J. and Akabas, M. H. (2010) Transmembrane segment 11 appears to line the purine permeation pathway of the Plasmodium falciparum equilibrative nucleoside transporter 1 (PfENT1). J. Biol. Chem. 285, 17001-17010
85. El Bissati, K., Zufferey, R., Witola, W. H., Carter, N. S., Ullman, B. and Ben Mamoun, C. (2006) The plasma membrane permease PfNT1 is essential for purine salvage in the human malaria parasite Plasmodium falciparum. Proc. Natl. Acad. Sci. U.S.A. 103, 9286-9291
86. El Bissati, K., Downie, M. J., Kim, S. K., Horowitz, M., Carter, N., Ullman, B. and Ben Mamoun, C. (2008) Genetic evidence for the essential role of PfNT1 in the transport and utilization of xanthine, guanine, guanosine and adenine by Plasmodium falciparum. Mol. Biochem. Parasitol. 161, 130-139
87. Quashie, N. B., Dorin-Semblat, D., Bray, P. G., Biagini, G. A., Doerig, C., Ranford-Cartwright, L. C. and De Koning, H. P. (2008) A comprehensive model of purine uptake by the malaria parasite Plasmodium falciparum: identification of four purine transport activities in intraerythrocytic parasites. Biochem. J. 411, 287-295
88. Frame, I. J., Merino, E. F., Schramm, V. L., Cassera, M. B. and Akabas, M. H. (2012) Malaria parasite type 4 equilibrative nucleoside transporters (ENT4) are purine transporters with distinct substrate specificity. Biochem. J. 446, 179-190
89. Downie, M. J., El Bissati, K., Bobenchik, A. M., Nic Lochlainn, L., Amerik, A., Zufferey, R., Kirk, K. and Ben Mamoun, C. (2010) PfNT2, a permease of the equilibrative nucleoside transporter family in the endoplasmic reticulum of Plasmodium falciparum. J. Biol. Chem. 285, 20827-20833
90. Choi, I. and Mikkelsen, R. B. (1990) Plasmodium falciparum: ATP/ADP transport across the parasitophorous vacuolar and plasma membranes. Exp. Parasitol. 71, 452-462
91. + -pyrophosphatase. J. Biol. Chem. 278, 5605-5612
92. Kanaani, J. and Ginsburg, H. (1989) Metabolic interconnection between the human malarial parasite Plasmodium falciparum and its host erythrocyte. Regulation of ATP levels by means of an adenylate translocator and adenylate kinase. J. Biol. Chem. 264, 3194-3199
93. Cassera, M. B., Hazleton, K. Z., Riegelhaupt, P. M., Merino, E. F., Luo, M., Akabas, M. H. and Schramm, V. L. (2008) Erythrocytic adenosine monophosphate as an alternative purine source in Plasmodium falciparum. J. Biol. Chem. 283, 32889-32899
94. Elford, B. C., Haynes, J. D., Chulay, J. D. and Wilson, R. J. (1985) Selective stage-specific changes in the permeability to small hydrophilic solutes of human erythrocytes infected with Plasmodium falciparum. Mol. Biochem. Parasitol. 16, 43-60
95. Sherman, I. W. (1977) Transport of amino acids and nucleic acid precursors in malarial parasites. Bull. W.H.O. 55, 211-225
96. Liu, J., Istvan, E. S., Gluzman, I. Y., Gross, J. and Goldberg, D. E. (2006) Plasmodium falciparum ensures its amino acid supply with multiple acquisition pathways and redundant proteolytic enzyme systems. Proc. Natl. Acad. Sci. U.S.A. 103, 8840-8845
97. Lew, V. L., Macdonald, L., Ginsburg, H., Krugliak, M. and Tiffert, T. (2004) Excess haemoglobin digestion by malaria parasites: A strategy to prevent premature host cell lysis. Blood Cells, Mol., Dis. 32, 353-359
98. Allen, R. J. and Kirk, K. (2004) Cell volume control in the Plasmodium-infected erythrocyte. Trends Parasitol. 20, 7-10
99. Tunnicliff, G. (1994) Amino acid transport by human erythrocyte membranes. Comp. Biochem. Physiol. Comp. Physiol. 108, 471-478
100. Siddiqui, W. A. and Schnell, J. V. (1972) In vitro and in vivo studies with Plasmodium falciparum and Plasmodium knowlesi. Proc. Helminthol. Soc. Wash. 39, 204-210
101. Teng, R., Junankar, P. R., Bubb, W. A., Rae, C., Mercier, P. and Kirk, K. (2009) Metabolite profiling of the intraerythrocytic malaria parasite Plasmodium falciparum by 1H NMR spectroscopy. NMR Biomed. 22, 292-302
102. Bozdech, Z., Llinas, M., Pulliam, B. L., Wong, E. D., Zhu, J. and DeRisi, J. L. (2003) The transcriptome of the intraerythrocytic developmental cycle of Plasmodium falciparum. PLoS Biol. 1, e5
103. Le Roch, K. G., Zhou, Y., Blair, P. L., Grainger, M., Moch, J. K., Haynes, J. D., De La Vega, P., Holder, A. A., Batalov, S., Carucci, D. J. and Winzeler, E. A. (2003) Discovery of gene function by expression profiling of the malaria parasite life cycle. Science 301, 1503-1508
104. Llinas, M., Bozdech, Z., Wong, E. D., Adai, A. T. and DeRisi, J. L. (2006) Comparative whole genome transcriptome analysis of three Plasmodium falciparum strains. Nucleic Acids Res. 34, 1166-1173
105. Skinner-Adams, T. S., Stack, C. M., Trenholme, K. R., Brown, C. L., Grembecka, J., Lowther, J., Mucha, A., Drag, M., Kafarski, P., McGowan, S. et al. (2010) Plasmodium falciparum neutral aminopeptidases: new targets for anti-malarials. Trends Biochem. Sci. 35, 53-61
106. Martin, R. E. and Kirk, K. (2004) The malaria parasite's chloroquine resistance transporter is a member of the drug/metabolite transporter superfamily. Mol. Biol. Evol. 21, 1938-1949
107. Tran, C. V. and Saier, M. H. (2004) The principal chloroquine resistance protein of Plasmodium falciparum is a member of the drug/metabolite transporter superfamily. Microbiology 150, 1-3
108. Barrand, M. A., Winterberg, M., Ng, F., Nguyen, M., Kirk, K. and Hladky, S. B. (2012) Glutathione export from human erythrocytes and Plasmodium falciparum malaria parasites. Biochem. J. 448, 389-400
109. Klokouzas, A., Tiffert, T., van Schalkwyk, D., Wu, C. P., van Veen, H. W., Barrand, M. A. and Hladky, S. B. (2004) Plasmodium falciparum expresses a multidrug resistance-associated protein. Biochem. Biophys. Res. Commun. 321, 197-201
110. Raj, D. K., Mu, J., Jiang, H., Kabat, J., Singh, S., Sullivan, M., Fay, M. P., McCutchan, T. F. and Su, X. Z. (2009) Disruption of a Plasmodium falciparum multidrug resistance-associated protein (PfMRP) alters its fitness and transport of antimalarial drugs and glutathione. J. Biol. Chem. 284, 7687-7696
111. Kavishe, R. A., van den Heuvel, J. M., van de Vegte-Bolmer, M., Luty, A. J., Russel, F. G. and Koenderink, J. B. (2009) Localization of the ATP-binding cassette (ABC) transport proteins PfMRP1, PfMRP2, and PfMDR5 at the Plasmodium falciparum plasma membrane. Malar. J. 8, 205
112. Saliba, K. J. and Kirk, K. (1998) Uptake of an antiplasmodial protease inhibitor into Plasmodium falciparum-infected human erythrocytes via a parasite-induced pathway. Mol. Biochem. Parasitol. 94, 297-301
113. Martin, R. E., Marchetti, R. V., Cowan, A. I., Howitt, S. M., Broer, S. and Kirk, K. (2009) Chloroquine transport via the malaria parasite's chloroquine resistance transporter. Science 325, 1680-1682
114. Martin, R. E., Butterworth, A. S., Gardiner, D. L., Kirk, K., McCarthy, J. S. and Skinner-Adams, T. S. (2012) Saquinavir inhibits the malaria parasite's chloroquine resistance transporter. Antimicrob. Agents Chemother. 56, 2283-2289
115. Patzewitz, E. M., Salcedo-Sora, J. E., Wong, E. H., Sethia, S., Stocks, P. A., Maughan, S. C., Murray, J. A., Krishna, S., Bray, P. G., Ward, S. A. and Muller, S. (2012) Glutathione transport: A new role for PfCRT in chloroquine resistance. Antioxid. Redox Signaling 19, 683-695
116. Augagneur, Y., Jaubert, L., Schiovani, M., Pachikara, N., Garg, A., Usmani-Brown, S., Wesolowski, D., Zeller, S., Ghosal, A., Cornillot, E. et al. (2013) Identification and functional analysis of the primary pantothante transporter, PfPAT, of the human malaria parasite Plasmodium falciparum. J. Biol. Chem. 288, 20558-20567
117. Hyde, J. E. (2005) Exploring the folate pathway in Plasmodium falciparum. Acta Trop. 94, 191-206
118. Gregson, A. and Plowe, C. V. (2005) Mechanisms of resistance of malaria parasites to antifolates. Pharmacol. Rev. 57, 117-145
119. Wang, P., Wang, Q., Sims, P. F. and Hyde, J. E. (2007) Characterisation of exogenous folate transport in Plasmodium falciparum. Mol. Biochem. Parasitol. 154, 40-51
120. Zhang, Y., Merali, S. and Meshnick, S. R. (1992) p-Aminobenzoic acid transport by normal and Plasmodium falciparum-infected erythrocytes. Mol. Biochem. Parasitol. 52, 185-194
121. Branda, R. F., Anthony, B. K. and Jacob, H. S. (1978) The mechanism of 5-methyltetrahydrofolate transport by human erythrocytes. J. Clin. Invest. 61, 1270-1275
122. Salcedo-Sora, J. E., Ochong, E., Beveridge, S., Johnson, D., Nzila, A., Biagini, G. A., Stocks, P. A., O'Neill, P. M., Krishna, S., Bray, P. G. and Ward, S. A. (2011) The molecular basis of folate salvage in Plasmodium falciparum: characterization of two folate transporters. J. Biol. Chem. 286, 44659-44668
123. Wengelnik, K., Vidal, V., Ancelin, M. L., Cathiard, A. M., Morgat, J. L., Kocken, C. H., Calas, M., Herrera, S., Thomas, A. W. and Vial, H. J. (2002) A class of potent antimalarials and their specific accumulation in infected erythrocytes. Science 295, 1311-1314
124. Kirk, K., Wong, H. Y., Elford, B. C., Newbold, C. I. and Ellory, J. C. (1991) Enhanced choline and Rb+ transport in human erythrocytes infected with the malaria parasite Plasmodium falciparum. Biochem. J. 278, 521-525
125. Mizuno, Y., Kawazu, S. I., Kano, S., Watanabe, N., Matsuura, T. and Ohtomo, H. (2003) In vitro uptake of vitamin A by Plasmodium falciparum. Ann. Trop. Med. Parasitol. 97, 237-243
126. + -ATPase localized in plasma membranes of malaria parasite cells, Plasmodium falciparum, is involved in regional acidification of parasitized erythrocytes. J. Biol. Chem. 275, 34353-34358
127. + -ATPase. J. Biol. Chem. 274, 33213-33219
128. + exchanger. Mol. Biochem. Parasitol. 162, 96-99
129. + exchanger determines chloroquine uptake in Plasmodium falciparum. J. Biol. Chem. 140, 335-345
130. Nkrumah, L. J., Riegelhaupt, P. M., Moura, P., Johnson, D. J., Patel, J., Hayton, K., Ferdig, M. T., Wellems, T. E., Akabas, M. H. and Fidock, D. A. (2009) Probing the multifactorial basis of Plasmodium falciparum quinine resistance: evidence for a strain-specific contribution of the sodium-proton exchanger PfNHE. Mol. Biochem. Parasitol. 165, 122-131
131. + exchanger activity and quinine resistance. Mol. Biochem. Parasitol. 153, 48-58
132. + antiport of Plasmodium falciparum membrane. J. Cell. Physiol. 154, 527-534
133. + regulation in the malaria parasite Plasmodium falciparum involves the cation ATPase PfATP4 and is a target of the spiroindolone antimalarials. Cell Host Microbe 13, 227-237
134. + extrusion imposes an 'acid load' on the intraerythrocytic malaria parasite. Mol. Biochem. Parasitol. 189, 1-4
135. Henry, R. I., Cobbold, S. A., Allen, R. J., Khan, A., Hayward, R., Lehane, A. M., Bray, P. G., Howitt, S. M., Biagini, G. A., Saliba, K. J. and Kirk, K. (2010) An acid-loading chloride transport pathway in the intraerythrocytic malaria parasite, Plasmodium falciparum. J. Biol. Chem. 285, 18615-18626
136. + channel in Plasmodium berghei transmission revealed by targeted gene disruption. Proc. Natl. Acad. Sci. U.S.A. 105, 6398-6402
137. + channel from the malaria parasite Plasmodium falciparum. Biochem. Biophys. Res. Commun. 318, 477-484
138. Prole, D. L. and Marrion, N. V. (2012) Identification of putative potassium channel homologues in pathogenic protozoa. PLoS ONE 7, e32264
139. Waller, K. L., McBride, S. M., Kim, K. and McDonald, T. V. (2008) Characterization of two putative potassium channels in Plasmodium falciparum. Malar. J. 7, 19
140. Bennett, T. N., Kosar, A. D., Ursos, L. M., Dzekunov, S., Sidhu, A. B., Fidock, D. A. and Roepe, P. D. (2004) Drug resistance-associated PfCRT mutations confer decreased Plasmodium falciparum digestive vacuolar pH. Mol. Biochem. Parasitol. 133, 99-114
141. Hayward, R., Saliba, K. J. and Kirk, K. (2006) The pH of the digestive vacuole of Plasmodium falciparum is not associated with chloroquine resistance. J. Cell Sci. 119, 1016-1025
142. Klonis, N., Tan, O., Jackson, K., Goldberg, D., Klemba, M. and Tilley, L. (2007) Evaluation of pH during cytostomal endocytosis and vacuolar catabolism of haemoglobin in Plasmodium falciparum. Biochem. J. 407, 343-354
143. Kuhn, Y., Rohrbach, P. and Lanzer, M. (2007) Quantitative pH measurements in Plasmodium falciparum-infected erythrocytes using pHluorin. Cell. Microbiol. 9, 1004-1013
144. + leak from the digestive vacuole in chloroquine-resistant malaria parasites. J. Cell Sci. 121, 1624-1632
145. + leak from the malaria parasite's digestive vacuole. Antimicrob. Agents Chemother. 52, 4374-4380
146. van Schalkwyk, D. A., Saliba, K. J., Biagini, G. A., Bray, P. G. and Kirk, K. (2013) Loss of pH control in Plasmodium falciparum parasites subjected to oxidative stress. PLoS ONE 8, e58933
147. + -pyrophosphatases in malaria parasites. Mol. Biochem. Parasitol. 114, 183-195
148. 2+ entry into Plasmodium falciparum-infected blood cells. Am. J. Trop. Med. Hyg. 54, 464-470
149. + transport in Plasmodium falciparum-infected red cells. J. Membr. Biol. 172, 13-24
150. 2+ pool. Cell Calcium 33, 137-144
151. Alleva, L. M. and Kirk, K. (2001) Calcium regulation in the intraerythrocytic malaria parasite Plasmodium falciparum. Mol. Biochem. Parasitol. 117, 121-128
152. 2+ release from intracellular stores in the malaria parasite Plasmodium falciparum within infected red blood cells. J. Biol. Chem. 286, 5905-5912
153. Beraldo, F. H., Almeida, F. M., da Silva, A. M. and Garcia, C. R. (2005) Cyclic AMP and calcium interplay as second messengers in melatonin-dependent regulation of Plasmodium falciparum cell cycle. J. Cell Biol. 170, 551-557
154. Hotta, C. T., Gazarini, M. L., Beraldo, F. H., Varotti, F. P., Lopes, C., Markus, R. P., Pozzan, T. and Garcia, C. R. (2000) Calcium-dependent modulation by melatonin of the circadian rhythm in malarial parasites. Nat. Cell Biol. 2, 466-468
155. Eckstein-Ludwig, U., Webb, R. J., Van Goethem, I. D., East, J. M., Lee, A. G., Kimura, M., O'Neill, P. M., Bray, P. G., Ward, S. A. and Krishna, S. (2003) Artemisinins target the SERCA of Plasmodium falciparum. Nature 424, 957-961
156. Pulcini, S., Staines, H. M., Pittman, J. K., Slavic, K., Doerig, C., Halbert, J., Tewari, R., Shah, F., Avery, M. A., Haynes, R. K. and Krishna, S. (2013) Expression in yeast links field polymorphisms in PfATP6 to in vitro artemisinin resistance and identifies new inhibitor classes. J. Infect. Dis. 208, 468-478
157. Garcia, C. R., Ann, S. E., Tavares, E. S., Dluzewski, A. R., Mason, W. T. and Paiva, F. B. (1998) Acidic calcium pools in intraerythrocytic malaria parasites. Eur. J. Cell Biol. 76, 133-138
158. + -pyrophosphatase in malaria parasites. Biochem. J. 347, 243-253
159. Ruiz, F. A., Luo, S., Moreno, S. N. and Docampo, R. (2004) Polyphosphate content and fine structure of acidocalcisomes of Plasmodium falciparum. Microsc. Microanal. 10, 563-567
160. 2+ store. J. Biol. Chem. 278, 27910-27915
161. Rohrbach, P., Friedrich, O., Hentschel, J., Plattner, H., Fink, R. H. and Lanzer, M. (2005) Quantitative calcium measurements in subcellular compartments of Plasmodium falciparum-infected erythrocytes. J. Biol. Chem. 280, 27960-27969
162. 2+ -ATPase (PfATP4) belonging to a subclass unique to apicomplexan organisms. J. Biol. Chem. 276, 10782-10787
163. + antiporter in Plasmodium falciparum. Mol. Microbiol. 76, 1591-1606
164. + antiporter. Malar. J. 11, 254
165. 2+ during sexual development. PLoS Pathog. 9, e1003191
166. Rasoloson, D., Shi, L., Chong, C. R., Kafsack, B. F. and Sullivan, D. J. (2004) Copper pathways in Plasmodium falciparum infected erythrocytes indicate an efflux role for the copper P-ATPase. Biochem. J. 381, 803-811
167. Rosenberg, E., Litus, I., Schwarzfuchs, N., Sinay, R., Schlesinger, P., Golenser, J., Baumeister, S., Lingelbach, K. and Pollack, Y. (2006) pfmdr2 confers heavy metal resistance to Plasmodium falciparum. J. Biol. Chem. 281, 27039-27045
168. Rosental, B., Hadad, U., Sinay, R., Braiman, A., Porgador, A. and Pollack, Y. (2012) Dual fluorescent labelling of the human malaria parasite Plasmodium falciparum for the analysis of the ABC type transporter pfmdr2 . Malar. J. 11, 371
169. Zalis, M. G., Wilson, C. M., Zhang, Y. and Wirth, D. F. (1993) Characterization of the pfmdr2 gene for Plasmodium falciparum. Mol. Biochem. Parasitol. 62, 83-92
170. Rubio, J. P. and Cowman, A. F. (1994) Plasmodium falciparum: the pfmdr2 protein is not overexpressed in chloroquine-resistant isolates of the malaria parasite. Exp. Parasitol. 79, 137-147
171. Briolant, S., Bogreau, H., Gil, M., Bouchiba, H., Baret, E., Amalvict, R., Rogier, C. and Pradines, B. (2012) The F423Y mutation in the pfmdr2 gene and mutations N51I, C59R, and S108N in the pfdhfr gene are independently associated with pyrimethamine resistance in Plasmodium falciparum isolates. Antimicrob. Agents Chemother. 56, 2750-2752
172. Ekong, R. M., Robson, K. J., Baker, D. A. and Warhurst, D. C. (1993) Transcripts of the multidrug resistance genes in chloroquine-sensitive and chloroquine-resistant Plasmodium falciparum. Parasitology 106, 107-115
173. Shoemaker, D. G., Bender, C. A. and Gunn, R. B. (1988) Sodium-phosphate cotransport in human red blood cells. Kinetics and role in membrane metabolism. J. Gen. Physiol. 92, 449-474
174. Lisk, G., Pain, M., Gluzman, I. Y., Kambhampati, S., Furuya, T., Su, X. Z., Fay, M. P., Goldberg, D. E. and Desai, S. A. (2008) Changes in the plasmodial surface anion channel reduce leupeptin uptake and can confer drug resistance in Plasmodium falciparum-infected erythrocytes. Antimicrob. Agents Chemother. 52, 2346-2354
175. Stead, A. M., Bray, P. G., Edwards, I. G., DeKoning, H. P., Elford, B. C., Stocks, P. A. and Ward, S. A. (2001) Diamidine compounds: Selective uptake and targeting in Plasmodium falciparum. Mol. Pharmacol. 59, 1298-1306
176. Biagini, G. A., Richier, E., Bray, P. G., Calas, M., Vial, H. and Ward, S. A. (2003) Heme binding contributes to antimalarial activity of bis-quaternary ammoniums. Antimicrob. Agents Chemother. 47, 2584-2589
177. Hill, D. A., Pillai, A. D., Nawaz, F., Hayton, K., Doan, L., Lisk, G. and Desai, S. A. (2007) A blasticidin S-resistant Plasmodium falciparum mutant with a defective plasmodial surface anion channel. Proc. Natl. Acad. Sci. U.S.A. 104, 1063-1068
178. Baumeister, S., Wiesner, J., Reichenberg, A., Hintz, M., Bietz, S., Harb, O. S., Roos, D. S., Kordes, M., Friesen, J., Matuschewski, K. et al. (2011) Fosmidomycin uptake into Plasmodium and Babesia -infected erythrocytes is facilitated by parasite-induced new permeability pathways. PLoS ONE 6, e19334
179. Sanchez, C. P., Dave, A., Stein, W. D. and Lanzer, M. (2010) Transporters as mediators of drug resistance in Plasmodium falciparum. Int. J. Parasitol. 40, 1109-1118
180. Fitch, C. D. (1970) Plasmodium falciparum in owl monkeys: drug resistance and chloroquine binding capacity. Science 169, 289-290
181. Cooper, R. A., Ferdig, M. T., Su, X. Z., Ursos, L. M., Mu, J., Nomura, T., Fujioka, H., Fidock, D. A., Roepe, P. D. and Wellems, T. E. (2002) Alternative mutations at position 76 of the vacuolar transmembrane protein PfCRT are associated with chloroquine resistance and unique stereospecific quinine and quinidine responses in Plasmodium falciparum. Mol. Pharmacol. 61, 35-42
182. Fidock, D. A., Nomura, T., Talley, A. K., Cooper, R. A., Dzekunov, S. M., Ferdig, M. T., Ursos, L. M., Sidhu, A. B., Naude, B., Deitsch, K. W. et al. (2000) Mutations in the P. falciparum digestive vacuole transmembrane protein PfCRT and evidence for their role in chloroquine resistance. Mol. Cell 6, 861-871
183. Sanchez, C. P., McLean, J. E., Rohrbach, P., Fidock, D. A., Stein, W. D. and Lanzer, M. (2005) Evidence for a pfcrt -associated chloroquine efflux system in the human malarial parasite Plasmodium falciparum. Biochemistry 44, 9862-9870
184. Papakrivos, J., Sa, J. M. and Wellems, T. E. (2012) Functional characterization of the Plasmodium falciparum chloroquine-resistance transporter (PfCRT) in transformed Dictyostelium discoideum vesicles. PLoS ONE 7, e39569
185. Sidhu, A. B., Verdier-Pinard, D. and Fidock, D. A. (2002) Chloroquine resistance in Plasmodium falciparum malaria parasites conferred by pfcrt mutations. Science 298, 210-213
186. Yuan, J., Cheng, K. C., Johnson, R. L., Huang, R., Pattaradilokrat, S., Liu, A., Guha, R., Fidock, D. A., Inglese, J., Wellems, T. E. et al. (2011) Chemical genomic profiling for antimalarial therapies, response signatures, and molecular targets. Science 333, 724-729
187. Lehane, A. M. and Kirk, K. (2010) Efflux of a range of antimalarial drugs and 'chloroquine resistance reversers' from the digestive vacuole in malaria parasites with mutant PfCRT. Mol. Microbiol. 77, 1039-1051
188. Sanchez, C. P., Stein, W. D. and Lanzer, M. (2008) Dissecting the components of quinine accumulation in Plasmodium falciparum. Mol. Microbiol. 67, 1081-1093
189. Waller, K. L., Muhle, R. A., Ursos, L. M., Horrocks, P., Verdier-Pinard, D., Sidhu, A. B., Fujioka, H., Roepe, P. D. and Fidock, D. A. (2003) Chloroquine resistance modulated in vitro by expression levels of the Plasmodium falciparum chloroquine resistance transporter. J. Biol. Chem. 278, 33593-33601
190. Reed, M. B., Saliba, K. J., Caruana, S. R., Kirk, K. and Cowman, A. F. (2000) Pgh1 modulates sensitivity and resistance to multiple antimalarials in Plasmodium falciparum. Nature 403, 906-909
191. Sidhu, A. B., Valderramos, S. G. and Fidock, D. A. (2005) pfmdr1 mutations contribute to quinine resistance and enhance mefloquine and artemisinin sensitivity in Plasmodium falciparum. Mol. Microbiol. 57, 913-926
192. Cowman, A. F., Karcz, S., Galatis, D. and Culvenor, J. G. (1991) A P-glycoprotein homologue of Plasmodium falciparum is localized on the digestive vacuole. J. Cell Biol. 113, 1033-1042
193. Karcz, S. R., Galatis, D. and Cowman, A. F. (1993) Nucleotide binding properties of a P-glycoprotein homologue from Plasmodium falciparum. Mol. Biochem. Parasitol. 58, 269-276
194. Rohrbach, P., Sanchez, C. P., Hayton, K., Friedrich, O., Patel, J., Sidhu, A. B., Ferdig, M. T., Fidock, D. A. and Lanzer, M. (2006) Genetic linkage of pfmdr1 with food vacuolar solute import in Plasmodium falciparum. EMBO J. 25, 3000-3011
195. Ecker, A., Lehane, A. M. and Fidock, D. A. (2012) Molecular markers of Plasmodium resistance to antimalarials. In Treatment and Prevention of Malaria - Antimalarial Drug Chemistry, Action and Use (Staines, H. M. and Krishna, S., eds), pp. 249-280, Springer, Basel
196. Sanchez, C. P., Rotmann, A., Stein, W. D. and Lanzer, M. (2008) Polymorphisms within PfMDR1 alter the substrate specificity for anti-malarial drugs in Plasmodium falciparum. Mol. Microbiol. 70, 786-798
197. Saliba, K. J., Lehane, A. M. and Kirk, K. (2008) A polymorphic drug pump in the malaria parasite. Mol. Microbiol. 70, 775-779
198. Lehane, A. M., van Schalkwyk, D. A., Valderramos, S. G., Fidock, D. A. and Kirk, K. (2011) Differential drug efflux or accumulation does not explain variation in the chloroquine response of Plasmodium falciparum strains expressing the same isoform of mutant PfCRT. Antimicrob. Agents Chemother. 55, 2310-2318
199. Sanchez, C. P., Mayer, S., Nurhasanah, A., Stein, W. D. and Lanzer, M. (2011) Genetic linkage analyses redefine the roles of PfCRT and PfMDR1 in drug accumulation and susceptibility in Plasmodium falciparum. Mol. Microbiol. 82, 865-878
200. Summers, R. L., Nash, M. N. and Martin, R. E. (2012) Know your enemy: understanding the role of PfCRT in drug resistance could lead to new antimalarial tactics. Cell. Mol. Life Sci. 69, 1967-1995
201. Dahlstrom, S., Ferreira, P. E., Veiga, M. I., Sedighi, N., Wiklund, L., Martensson, A., Farnert, A., Sisowath, C., Osorio, L., Darban, H. et al. (2009) Plasmodium falciparum multidrug resistance protein 1 and artemisinin-based combination therapy in Africa. J. Infect. Dis. 200, 1456-1464
202. Dahlstrom, S., Veiga, M. I., Martensson, A., Bjorkman, A. and Gil, J. P. (2009) Polymorphism in PfMRP1 (Plasmodium falciparum multidrug resistance protein 1) amino acid 1466 associated with resistance to sulfadoxine- pyrimethamine treatment. Antimicrob. Agents Chemother. 53, 2553-2556
203. Veiga, M. I., Ferreira, P. E., Jornhagen, L., Malmberg, M., Kone, A., Schmidt, B. A., Petzold, M., Bjorkman, A., Nosten, F. and Gil, J. P. (2011) Novel polymorphisms in Plasmodium falciparum ABC transporter genes are associated with major ACT antimalarial drug resistance. PLoS ONE 6, e20212
204. Veiga, M. I., Ferreira, P. E., Schmidt, B. A., Ribacke, U., Bjorkman, A., Tichopad, A. and Gil, J. P. (2010) Antimalarial exposure delays Plasmodium falciparum intra-erythrocytic cycle and drives drug transporter genes expression. PLoS ONE 5, e12408
205. Ferdig, M. T., Cooper, R. A., Mu, J., Deng, B., Joy, D. A., Su, X. Z. and Wellems, T. E. (2004) Dissecting the loci of low-level quinine resistance in malaria parasites. Mol. Microbiol. 52, 985-997
206. Okombo, J., Ohuma, E., Picot, S. and Nzila, A. (2011) Update on genetic markers of quinine resistance in Plasmodium falciparum. Mol. Biochem. Parasitol. 177, 77-82
207. Rottmann, M., McNamara, C., Yeung, B. K., Lee, M. C., Zou, B., Russell, B., Seitz, P., Plouffe, D. M., Dharia, N. V., Tan, J. et al. (2010) Spiroindolones, a potent compound class for the treatment of malaria. Science 329, 1175-1180
208. Krishna, S., Pulcini, S., Fatih, F. and Staines, H. (2010) Artemisinins and the biological basis for the PfATP6/SERCA hypothesis. Trends Parasitol. 26, 517-523
209. Woodrow, C. J. and Bustamante, L. Y. (2011) Mechanisms of artemisinin action and resistance: wider focus is needed. Trends Parasitol. 27, 2-3
210. Mu, J., Ferdig, M. T., Feng, X., Joy, D. A., Duan, J., Furuya, T., Subramanian, G., Aravind, L., Cooper, R. A., Wootton, J. C. et al. (2003) Multiple transporters associated with malaria parasite responses to chloroquine and quinine. Mol. Microbiol. 49, 977-989
211. Mu, J., Myers, R. A., Jiang, H., Liu, S., Ricklefs, S., Waisberg, M., Chotivanich, K., Wilairatana, P., Krudsood, S., White, N. J. et al. (2010) Plasmodium falciparum genome-wide scans for positive selection, recombination hot spots and resistance to antimalarial drugs. Nat. Genet. 42, 268-271
212. Park, D. J., Lukens, A. K., Neafsey, D. E., Schaffner, S. F., Chang, H. H., Valim, C., Ribacke, U., Van Tyne, D., Galinsky, K., Galligan, M. et al. (2012) Sequence-based association and selection scans identify drug resistance loci in the Plasmodium falciparum malaria parasite. Proc. Natl. Acad. Sci. U.S.A. 109, 13052-13057
213. Van Tyne, D., Park, D. J., Schaffner, S. F., Neafsey, D. E., Angelino, E., Cortese, J. F., Barnes, K. G., Rosen, D. M., Lukens, A. K., Daniels, R. F. et al. (2011) Identification and functional validation of the novel antimalarial resistance locus PF10-0355 in Plasmodium falciparum. PLoS Genet. 7, e1001383
214. Mullin, K. A., Lim, L., Ralph, S. A., Spurck, T. P., Handman, E. and McFadden, G. I. (2006) Membrane transporters in the relict plastid of malaria parasites. Proc. Natl. Acad. Sci. U.S.A. 103, 9572-9577
215. van Dooren, G. G., Su, V., D'Ombrain, M. C. and McFadden, G. I. (2002) Processing of an apicoplast leader sequence in Plasmodium falciparum and the identification of a putative leader cleavage enzyme. J. Biol. Chem. 277, 23612-23619
216. Lim, L., Linka, M., Mullin, K. A., Weber, A. P. and McFadden, G. I. (2010) The carbon and energy sources of the non-photosynthetic plastid in the malaria parasite. FEBS Lett. 584, 549-554
217. Boisson, B., Lacroix, C., Bischoff, E., Gueirard, P., Bargieri, D. Y., Franke-Fayard, B., Janse, C. J., Menard, R. and Baldacci, P. (2011) The novel putative transporter NPT1 plays a critical role in early stages of Plasmodium berghei sexual development. Mol. Microbiol. 81, 1343-1357
218. Eastman, R. T., Pattaradilokrat, S., Raj, D. K., Dixit, S., Deng, B., Miura, K., Yuan, J., Tanaka, T. Q., Johnson, R. L., Jiang, H. et al. (2013) A class of tricyclic compounds blocking malaria parasite oocyst development and transmission. Antimicrob. Agents Chemother. 57, 425-435
219. Beitz, E., Pavlovic-Djuranovic, S., Yasui, M., Agre, P. and Schultz, J. E. (2004) Molecular dissection of water and glycerol permeability of the aquaglyceroporin from Plasmodium falciparum by mutational analysis. Proc. Natl. Acad. Sci. U.S.A. 101, 1153-1158
220. Pavlovic-Djuranovic, S., Kun, J. F. J., Schultz, J. E. and Beitz, E. (2006) Dihydroxyacetone and methylglyoxal as permeants of the Plasmodium aquaglyceroporin inhibit parasite proliferation. Biochim. Biophys. Acta 1758, 1012-1017
221. Zeuthen, T., Wu, B., Pavlovic-Djuranovic, S., Holm, L. M., Uzcategui, N. L., Kun, J. F. J., Schultz, J. E. and Beitz, E. (2006) Ammonia permeability of the aquaglyceroporins from Plasmodium falciparum, Toxoplasma gondii and Trypansoma brucei. Mol. Microbiol. 61, 1598-1608
222. Choveaux, D. L., Przyborski, J. M. and Goldring, J. P. D. (2012) A Plasmodium falciparum, copper-binding membrane protein with copper transport motifs. Malaria J. 11, 397