Resistance of a rodent malaria parasite to a thymidylate synthase inhibitor induces an apoptotic parasite death and imposes a huge cost of fitness

PLoS ONE

Volumn 6, Issue 6, 2011, Pages

  Muregi, Francis W ^a,b   Ohta, Isao ^a   Masato, Uchijima ^a   Kino, Hideto ^a   Ishih, Akira ^a  

^a HAMAMATSU UNIVERSITY SCHOOL OF MEDICINE   (Japan)

^b KENYA MEDICAL RESEARCH INSTITUTE   (Kenya)

Author keywords

[No Author keywords available]

Indexed keywords

FLUOROOROTIC ACID; PYRIMETHAMINE; ENZYME INHIBITOR; THYMIDYLATE SYNTHASE;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANTIBIOTIC RESISTANCE; APOPTOSIS; ARTICLE; CELL PROLIFERATION; CONTROLLED STUDY; DNA FRAGMENTATION; DRUG EFFICACY; DRUG SENSITIVITY; DRUG STABILITY; MALARIA CONTROL; MALE; MICROSCOPY; MOUSE; NONHUMAN; PARASITEMIA; PLASMODIUM BERGHEI; POLYACRYLAMIDE GEL ELECTROPHORESIS; RODENT MALARIA; TRANSMISSION ELECTRON MICROSCOPY; ANIMAL; CYTOLOGY; DRUG ANTAGONISM; DRUG EFFECT; PATHOGENICITY;

METAZOA; MUS; PLASMODIUM FALCIPARUM; PROTISTA; PROTOZOA; RODENTIA;

ANIMALS; APOPTOSIS; ELECTROPHORESIS, POLYACRYLAMIDE GEL; ENZYME INHIBITORS; MICE; MICROSCOPY, ELECTRON, TRANSMISSION; PLASMODIUM BERGHEI; THYMIDYLATE SYNTHASE;

EID: 79959206368     PISSN: None     EISSN: 19326203     Source Type: Journal    
DOI: 10.1371/journal.pone.0021251     Document Type: Article

References (114)

1. Schlitzer M, (2007) Malaria chemotherapeutics part I: History of antimalarial drug development, currently used therapeutics, and drugs in clinical development. Chem Med Chem 2: 944-986.
2. Noedl H, Se Y, Schaecher K, Smith BL, Socheat D, et al. (2008) Evidence of artemisinin-resistant malaria in western Cambodia. N Engl J Med 359: 2619-2620.
3. Grech K, Watt K, Read AF, (2006) Host-parasite interactions for virulence and resistance in a malaria model system. J Evol Biol 19: 1620-1630.
4. Mackinnon MJ, Read AF, (2004) Immunity promotes virulence evolution in a malaria model. PLoS Biol 2: E230.
5. Hastings IM, Watkins WM, (2006) Tolerance is the key to understanding antimalarial drug resistance. Trends Parasitol 22: 71-77.
6. Gatton ML, Hogarth W, Saul A, (2001) Time of treatment influences the appearance of drug-resistant parasites in Plasmodium falciparum infections. Parasitology 123: 537-546.
7. Schneider P, Chan BH, Reece SE, Read AF, (2008) Does the drug sensitivity of malaria parasites depend on their virulence? Malar J 7: 257.
8. Walliker D, (2005) The hitchhiker's guide to malaria parasite genes. Trends Parasitol 21: 489-493.
9. Hastings IM, (2003) Malaria control and the evolution of drug resistance: an intriguing link. Trends Parasitol 19: 70-73.
10. Rathod PK, Leffers NP, Young RD, (1992) Molecular targets of 5-fluoroorotate in the human malaria parasite, Plasmodium falciparum. Antimicrob Agents Chemother 36: 704-711.
11. Gutteridge WE, Trigg PI, (1970) Incorporation of radioactive precursors into DNA and RNA of Plasmodium knowlesi in vitro. J Protozool 17: 89-96.
12. Yuvaniyama J, Chitnumsub P, Kamchonwongpaisan S, Vanichtanankul J, Sirawaraporn W, et al. (2003) Insights into antifolate resistance from malarial DHFR-TS structures. Nat Struct Biol 10: 357-365.
13. Ivanetich KM, Santi DV, (1990) Bifunctional thymidylate synthase-dihydrofolate reductase in protozoa. Faseb J 4: 1591-1597.
14. Villalba JD, Gomez C, Medel O, Sanchez V, Carrero JC, et al. (2007) Programmed cell death in Entamoeba histolytica induced by the aminoglycoside G418. Microbiology 153: 3852-3863.
15. Allen RT, Hunter WJ 3rd, Agrawal DK, (1997) Morphological and biochemical characterization and analysis of apoptosis. J Pharmacol Toxicol Methods 37: 215-228.
16. Welburn SC, Barcinski MA, Williams GT, (1997) Programmed cell death in trypanosomatids. Parasitol Today 13: 22-26.
17. Baton LA, Warr E, Hoffman SA, Dimopoulos G, (2008) Programmed cell death during malaria parasite infection of the vertebrate host and mosquito vector. Programmed Cell Death in Protozoa New York Landes Bioscience, Springer pp. 74-90.
18. Holzmuller P, Sereno D, Cavaleyra M, Mangot I, Daulouede S, et al. (2002) Nitric oxide-mediated proteasome-dependent oligonucleosomal DNA fragmentation in Leishmania amazonensis amastigotes. Infect Immun 70: 3727-3735.
19. De Souza EM, Menna-Barreto R, Araujo-Jorge TC, Kumar A, Hu Q, et al. (2006) Antiparasitic activity of aromatic diamidines is related to apoptosis-like death in Trypanosoma cruzi. Parasitology 133: 75-79.
20. Chose O, Sarde CO, Noel C, Gerbod D, Jimenez JC, et al. (2003) Cell death in protists without mitochondria. Ann N Y Acad Sci 1010: 121-125.
21. Kobayashi T, Endoh H, (2003) Caspase-like activity in programmed nuclear death during conjugation of Tetrahymena thermophila. Cell Death Differ 10: 634-640.
22. Ramos E, Olivos-Garcia A, Nequiz M, Saavedra E, Tello E, et al. (2007) Entamoeba histolytica: apoptosis induced in vitro by nitric oxide species. Exp Parasitol 116: 257-265.
23. Nasirudeen AM, Hian YE, Singh M, Tan KS, (2004) Metronidazole induces programmed cell death in the protozoan parasite Blastocystis hominis. Microbiology 150: 33-43.
24. Picot S, Burnod J, Bracchi V, Chumpitazi BF, Ambroise-Thomas P, (1997) Apoptosis related to chloroquine sensitivity of the human malaria parasite Plasmodium falciparum. Trans R Soc Trop Med Hyg 91: 590-591.
25. Meslin B, Barnadas C, Boni V, Latour C, De Monbrison F, et al. (2007) Features of apoptosis in Plasmodium falciparum erythrocytic stage through a putative role of PfMCA1 metacaspase-like protein. J Infect Dis 195: 1852-1859.
26. Al-Olayan EM, Williams GT, Hurd H, (2002) Apoptosis in the malaria protozoan, Plasmodium berghei: a possible mechanism for limiting intensity of infection in the mosquito. Int J Parasitol 32: 1133-1143.
27. Sat B, Hazan R, Fisher T, Khaner H, Glaser G, et al. (2001) Programmed cell death in Escherichia coli: some antibiotics can trigger mazEF lethality. J Bacteriol 183: 2041-2045.
28. Madeo F, Frohlich E, Ligr M, Grey M, Sigrist SJ, et al. (1999) Oxygen stress: a regulator of apoptosis in yeast. J Cell Biol 145: 757-767.
29. Cornillon S, Foa C, Davoust J, Buonavista N, Gross JD, et al. (1994) Programmed cell death in Dictyostelium. J Cell Sci 107 (Pt 10): 2691-2704.
30. Vardi A, Berman-Frank I, Rozenberg T, Hadas O, Kaplan A, et al. (1999) Programmed cell death of the dinoflagellate Peridinium gatunense is mediated by CO(2) limitation and oxidative stress. Curr Biol 9: 1061-1064.
31. Scheuerlein R, Treml S, Thar B, Tirlapur UK, Hader DP, (1995) Evidence for UV-B-induced DNA degradation in Euglena gracilis mediated by activation of metal-dependent nucleases. J Photochem Photobiol B 31: 113-123.
32. Muregi FW, Kino H, Ishih A, (2008) Plasmodium berghei: lack of antimalarial activity of an analogue of folate precursor, 2,4-diamino-6-hydroxymethylpteridine in a mouse model. Exp Parasitol 120: 286-289.
33. Peters W, Robinson BL, (1999) The chemotherapy of rodent malaria. LVI. Studies on the development of resistance to natural and synthetic endoperoxides. Ann Trop Med Parasitol 93: 325-329.
34. Peters W, Robinson BL, (2000) The chemotherapy of rodent malaria. LVIII. Drug combinations to impede the selection of drug resistance, Part. 2: The new generation-artemisinin or artesunate with long-acting blood schizontocides. Ann Trop Med Parasitol 94: 23-35.
35. Benoit-Vical F, Lelievre J, Berry A, Deymier C, Dechy-Cabaret O, et al. (2007) Trioxaquines are new antimalarial agents active on all erythrocytic forms, including gametocytes. Antimicrob Agents Chemother 51: 1463-1472.
36. Muregi FW, Ishih A, Suzuki T, Kino H, Amano T, et al. (2007) In vivo antimalarial activity of aqueous extracts from Kenyan medicinal plants and their chloroquine (CQ) potentiation effects against a blood-induced CQ-resistant rodent parasite in mice. Phytother Res 21: 337-343.
37. Giha HA, Elbashir MI, A-Elbasit IE, A-Elgadir TME, ElGhazali GE, et al. (2006) Drug resistance-virulence relationship in Plasmodium falciparum causing severe malaria in an area of seasonal and unstable transmission. Acta Trop 97: 181-187.
38. Stein WD, Sanchez CP, Lanzer M, (2009) Virulence and drug resistance in malaria parasites. Trends Parasitol 25: 441-443.
39. Totino PR, Daniel-Ribeiro CT, Corte-Real S, de Fatima Ferreira-da-Cruz M, (2008) Plasmodium falciparum: erythrocytic stages die by autophagic-like cell death under drug pressure. Exp Parasitol 118: 478-486.
40. Massimine KM, McIntosh MT, Doan LT, Atreya CE, Gromer S, et al. (2006) Eosin B as a novel antimalarial agent for drug-resistant Plasmodium falciparum. Antimicrob Agents Chemother 50: 3132-3141.
41. Cheng Q, Lawrence G, Reed C, Stowers A, Ranford-Cartwright L, et al. (1997) Measurement of Plasmodium falciparum growth rates in vivo: a test of malaria vaccines. Am J Trop Med Hyg 57: 495-500.
42. Hall N, Karras M, Raine JD, Carlton JM, Kooij TW, et al. (2005) A comprehensive survey of the Plasmodium life cycle by genomic, transcriptomic, and proteomic analyses. Science 307: 82-86.
43. Van Triest B, Pinedo HM, Giaccone G, Peters GJ, (2000) Downstream molecular determinants of response to 5-fluorouracil and antifolate thymidylate synthase inhibitors. Ann Oncol 11: 385-391.
44. Rathod PK, Khatri A, Hubbert T, Milhous WK, (1989) Selective activity of 5-fluoroorotic acid against Plasmodium falciparum in vitro. Antimicrob Agents Chemother 33: 1090-1094.
45. Rathod PK, Gomez ZM, (1991) Plasmodium yoelii: oral delivery of 5-fluoroorotate to treat malaria in mice. Exp Parasitol 73: 512-514.
46. Fisher TC, Milner AE, Gregory CD, Jackman AL, Aherne GW, et al. (1993) bcl-2 modulation of apoptosis induced by anticancer drugs: resistance to thymidylate stress is independent of classical resistance pathways. Cancer Res 53: 3321-3326.
47. Chu E, Voeller DM, Morrison PF, Jones KL, Takechi T, et al. (1994) The effect of reducing reagents on binding of thymidylate synthase protein to thymidylate synthase messenger RNA. J Biol Chem 269: 20289-20293.
48. Zhang K, Rathod PK, (2002) Divergent regulation of dihydrofolate reductase between malaria parasite and human host. Science 296: 545-547.
49. Cowman AF, Morry MJ, Biggs BA, Cross GA, Foote SJ, (1988) Amino acid changes linked to pyrimethamine resistance in the dihydrofolate reductase-thymidylate synthase gene of Plasmodium falciparum. Proc Natl Acad Sci U S A 85: 9109-9113.
50. Peterson DS, Walliker D, Wellems TE, (1988) Evidence that a point mutation in dihydrofolate reductase-thymidylate synthase confers resistance to pyrimethamine in falciparum malaria. Proc Natl Acad Sci U S A 85: 9114-9118.
51. Gregson A, Plowe CV, (2005) Mechanisms of resistance of malaria parasites to antifolates. Pharmacol Rev 57: 117-145.
52. Foote SJ, Galatis D, Cowman AF, (1990) Amino acids in the dihydrofolate reductase-thymidylate synthase gene of Plasmodium falciparum involved in cycloguanil resistance differ from those involved in pyrimethamine resistance. Proc Natl Acad Sci U S A 87: 3014-3017.
53. Rathod PK, Khosla M, Gassis S, Young RD, Lutz C, (1994) Selection and characterization of 5-fluoroorotate-resistant Plasmodium falciparum. Antimicrob Agents Chemother 38: 2871-2876.
54. Lauer SA, Rathod PK, Ghori N, Haldar K, (1997) A membrane network for nutrient import in red cells infected with the malaria parasite. Science 276: 1122-1125.
55. Akompong T, VanWye J, Ghori N, Haldar K, (1999) Artemisinin and its derivatives are transported by a vacuolar-network of Plasmodium falciparum and their anti-malarial activities are additive with toxic sphingolipid analogues that block the network. Mol Biochem Parasitol 101: 71-79.
56. Haldar K, Akompong T, (2001) Transport and Trafficking in Plasmodium-Infected Red cells. In: Rosenthal PJ, editors. Antimalarial Chemotherapy: Mechanisms of Action, Resistance, and New Directions in Drug Discovery Totowa, New Jersey Humana Press Inc pp. 27-41.
57. Srivastava IK, Morrisey JM, Darrouzet E, Daldal F, Vaidya AB, (1999) Resistance mutations reveal the atovaquone-binding domain of cytochrome b in malaria parasites. Mol Microbiol 33: 704-711.
58. Korsinczky M, Chen N, Kotecka B, Saul A, Rieckmann K, et al. (2000) Mutations in Plasmodium falciparum cytochrome b that are associated with atovaquone resistance are located at a putative drug-binding site. Antimicrob Agents Chemother 44: 2100-2108.
59. Schrag SJ, Perrot V, (1996) Reducing antibiotic resistance. Nature 381: 120-121.
60. Levin BR, Perrot V, Walker N, (2000) Compensatory mutations, antibiotic resistance and the population genetics of adaptive evolution in bacteria. Genetics 154: 985-997.
61. Bjorkman J, Hughes D, Andersson DI, (1998) Virulence of antibiotic-resistant Salmonella typhimurium. Proc Natl Acad Sci U S A 95: 3949-3953.
62. Bjorkman J, Andersson DI, (2000) The cost of antibiotic resistance from a bacterial perspective. Drug Resist Updat 3: 237-245.
63. Mariam DH, Mengistu Y, Hoffner SE, Andersson DI, (2004) Effect of rpoB mutations conferring rifampin resistance on fitness of Mycobacterium tuberculosis. Antimicrob Agents Chemother 48: 1289-1294.
64. Borman AM, Paulous S, Clavel F, (1996) Resistance of human immunodeficiency virus type 1 to protease inhibitors: selection of resistance mutations in the presence and absence of the drug. J Gen Virol 77 (Pt 3): 419-426.
65. Leigh Brown AJ, Frost SD, Mathews WC, Dawson K, Hellmann NS, et al. (2003) Transmission fitness of drug-resistant human immunodeficiency virus and the prevalence of resistance in the antiretroviral-treated population. J Infect Dis 187: 683-686.
66. Lu J, Sista P, Giguel F, Greenberg M, Kuritzkes DR, (2004) Relative replicative fitness of human immunodeficiency virus type 1 mutants resistant to enfuvirtide (T-20). J Virol 78: 4628-4637.
67. Fohl LM, Roos DS, (2003) Fitness effects of DHFR-TS mutations associated with pyrimethamine resistance in apicomplexan parasites. Mol Microbiol 50: 1319-1327.
68. Nagaev I, Bjorkman J, Andersson DI, Hughes D, (2001) Biological cost and compensatory evolution in fusidic acid-resistant Staphylococcus aureus. Mol Microbiol 40: 433-439.
69. Walliker D, Hunt P, Babiker H, (2005) Fitness of drug-resistant malaria parasites. Acta Trop 94: 251-259.
70. Hayward R, Saliba KJ, Kirk K, (2005) pfmdr1 mutations associated with chloroquine resistance incur a fitness cost in Plasmodium falciparum. Mol Microbiol 55: 1285-1295.
71. Kublin JG, Cortese JF, Njunju EM, Mukadam RA, Wirima JJ, et al. (2003) Reemergence of chloroquine-sensitive Plasmodium falciparum malaria after cessation of chloroquine use in Malawi. J Infect Dis 187: 1870-1875.
72. Mita T, Kaneko A, Lum JK, Bwijo B, Takechi M, et al. (2003) Recovery of chloroquine sensitivity and low prevalence of the Plasmodium falciparum chloroquine resistance transporter gene mutation K76T following the discontinuance of chloroquine use in Malawi. Am J Trop Med Hyg 68: 413-415.
73. Mita T, Kaneko A, Lum JK, Zungu IL, Tsukahara T, et al. (2004) Expansion of wild type allele rather than back mutation in pfcrt explains the recent recovery of chloroquine sensitivity of Plasmodium falciparum in Malawi. Mol Biochem Parasitol 135: 159-163.
74. Wang X, Mu J, Li G, Chen P, Guo X, et al. (2005) Decreased prevalence of the Plasmodium falciparum chloroquine resistance transporter 76T marker associated with cessation of chloroquine use against P. falciparum malaria in Hainan, People's Republic of China. Am J Trop Med Hyg 72: 410-414.
75. De-quan L, Rui-jun L, Dao-xing R, Da-qing G, Chun-yong Z, et al. (1995) Changes in the resistance of Plasmodium falciparum to chloroquine in Hainan, China. Bulletin of the World Health Organization 73: 483-486.
76. Thaithong S, Suebsaeng L, Rooney W, Beale GH, (1988) Evidence of increased chloroquine sensitivity in Thai isolates of Plasmodium falciparum. Trans R Soc Trop Med Hyg 82: 37-38.
77. Abdel-Muhsin AM, Mackinnon MJ, Ali E, Nassir el KA, Suleiman S, et al. (2004) Evolution of drug-resistance genes in Plasmodium falciparum in an area of seasonal malaria transmission in Eastern Sudan. J Infect Dis 189: 1239-1244.
78. Babiker HA, Satti G, Ferguson H, Bayoumi R, Walliker D, (2005) Drug resistant Plasmodium falciparum in an area of seasonal transmission. Acta Trop 94: 260-268.
79. Thanh NV, Cowman AF, Hipgrave D, Kim TB, Phuc BQ, et al. (2001) Assessment of susceptibility of Plasmodium falciparum to chloroquine, quinine, mefloquine, sulfadoxine-pyrimethamine and artemisinin in southern Viet Nam. Trans R Soc Trop Med Hyg 95: 513-517.
80. Huong NM, Hewitt S, Davis TM, Dao LD, Toan TQ, et al. (2001) Resistance of Plasmodium falciparum to antimalarial drugs in a highly endemic area of southern Viet Nam: a study in vivo and in vitro. Trans R Soc Trop Med Hyg 95: 325-329.
81. Nguyen MH, Davis TM, Cox-Singh J, Hewitt S, Tran QT, et al. (2003) Treatment of uncomplicated falciparum malaria in southern Vietnam: can chloroquine or sulfadoxine-pyrimethamine be reintroduced in combination with artesunate? Clin Infect Dis 37: 1461-1466.
82. Rosario VE, Hall R, Walliker D, Beale GH, (1978) Persistence of drug-resistant malaria parasites. Lancet 1: 185-187.
83. Shinondo CJ, Lanners HN, Lowrie RC Jr, Wiser MF, (1994) Effect of pyrimethamine resistance on sporogony in a Plasmodium berghei/Anopheles stephensi model. Exp Parasitol 78: 194-202.
84. Peters JM, Chen N, Gatton M, Korsinczky M, Fowler EV, et al. (2002) Mutations in cytochrome b resulting in atovaquone resistance are associated with loss of fitness in Plasmodium falciparum. Antimicrob Agents Chemother 46: 2435-2441.
85. Wyllie AH, (1980) Glucocorticoid-induced thymocyte apoptosis is associated with endogenous endonuclease activation. Nature 284: 555-556.
86. Oberhammer F, Wilson JW, Dive C, Morris ID, Hickman JA, et al. (1993) Apoptotic death in epithelial cells: cleavage of DNA to 300 and/or 50 kb fragments prior to or in the absence of internucleosomal fragmentation. Embo J 12: 3679-3684.
87. Muller A, Hacker J, Brand BC, (1996) Evidence for apoptosis of human macrophage-like HL-60 cells by Legionella pneumophila infection. Infect Immun 64: 4900-4906.
88. Garrity MM, Burgart LJ, Riehle DL, Hill EM, Sebo TJ, et al. (2003) Identifying and quantifying apoptosis: navigating technical pitfalls. Mod Pathol 16: 389-394.
89. Abend M, Schmelz HU, Kraft K, Rhein AP, van Beuningen D, et al. (1998) Intercomparison of apoptosis morphology with active DNA cleavage on single cells in vitro and on testis tumours. J Pathol 185: 419-426152.
90. Peters GJ, van Triest B, Backus HH, Kuiper CM, van der Wilt CL, et al. (2000) Molecular downstream events and induction of thymidylate synthase in mutant and wild-type p53 colon cancer cell lines after treatment with 5-fluorouracil and the thymidylate synthase inhibitor raltitrexed. Eur J Cancer 36: 916-924.
91. McGuire JJ, (2003) Anticancer antifolates: current status and future directions. Curr Pharm Des 9: 2593-2613.
92. Jackman AL, Calvert AH, (1995) Folate-based thymidylate synthase inhibitors as anticancer drugs. Ann Oncol 6: 871-881.
93. Curtin NJ, Harris AL, Aherne GW, (1991) Mechanism of cell death following thymidylate synthase inhibition: 2′-deoxyuridine-5′-triphosphate accumulation, DNA damage, and growth inhibition following exposure to CB3717 and dipyridamole. Cancer Res 51: 2346-2352.
94. Ayusawa D, Shimizu K, Koyama H, Takeishi K, Seno T, (1983) Accumulation of DNA strand breaks during thymineless death in thymidylate synthase-negative mutants of mouse FM3A cells. J Biol Chem 258: 12448-12454.
95. Yin MB, Guimaraes MA, Zhang ZG, Arredondo MA, Rustum YM, (1992) Time dependence of DNA lesions and growth inhibition by ICI D1694, a new quinazoline antifolate thymidylate synthase inhibitor. Cancer Res 52: 5900-5905.
96. Nippon Gene/Wako 2009-2010 Catalogue. Available: http://www.wako-chem.co.jp/siyaku/info/life/article/gene2007.htm. Accessed 2010 Nov 10.
97. Jacobson MD, Weil M, Raff MC, (1997) Programmed cell death in animal development. Cell 88: 347-354.
98. Kerr JF, Winterford CM, Harmon BV, (1994) Apoptosis. Its significance in cancer and cancer therapy. Cancer 73: 2013-2026.
99. Bursch W, Kleine L, Tenniswood M, (1990) The biochemistry of cell death by apoptosis. Biochem Cell Biol 68: 1071-1074.
100. Arends MJ, McGregor AH, Wyllie AH, (1994) Apoptosis is inversely related to necrosis and determines net growth in tumors bearing constitutively expressed myc, ras, and HPV oncogenes. Am J Pathol 144: 1045-1057.
101. Howie SE, Sommerfield AJ, Gray E, Harrison DJ, (1994) Peripheral T lymphocyte depletion by apoptosis after CD4 ligation in vivo: selective loss of CD44- and 'activating' memory T cells. Clin Exp Immunol 95: 195-200.
102. Arnot DE, Gull K, (1998) The Plasmodium cell-cycle: facts and questions. Ann Trop Med Parasitol 92: 361-365.
103. Newbold CI, Boyle DB, Smith CC, Brown KN, (1982) Stage specific protein and nucleic acid synthesis during the asexual cycle of the rodent malaria Plasmodium chabaudi. Mol Biochem Parasitol 5: 33-44.
104. Leiden Malaria Research Group (LMRG). P. berghei- Model of malaria. Available: http://www.lumc.nl/con/1040/81028091348221/810281121192556/811070740182556/. Accessed 2010 Nov 10.
105. Schetters TP, Hermsen CC, Van Zon AA, Eling WM, (1988) Stage-specific proteins of Plasmodium berghei-infected red blood cells detected by antibodies of immune mouse serum. Parasitol Res 75: 69-72.
106. Franke-Fayard B, Fonager J, Braks A, Khan SM, Janse CJ, (2010) Sequestration and tissue accumulation of human malaria parasites: can we learn anything from rodent models of malaria? PLoS Pathog 6.
107. Kempe DS, Akel A, Lang PA, Hermle T, Biswas R, et al. (2007) Suicidal erythrocyte death in sepsis. J Mol Med 85: 273-281.
108. Lang KS, Duranton C, Poehlmann H, Myssina S, Bauer C, et al. (2003) Cation channels trigger apoptotic death of erythrocytes. Cell Death Differ 10: 249-256.
109. Lang KS, Lang PA, Bauer C, Duranton C, Wieder T, et al. (2005) Mechanisms of suicidal erythrocyte death. Cell Physiol Biochem 15: 195-202.
110. Deponte M, Becker K, (2004) Plasmodium falciparum-do killers commit suicide? Trends Parasitol 20: 165-169.
111. Lines JD, Wilkes TJ, Lyimo EO, (1991) Human malaria infectiousness measured by age-specific sporozoite rates in Anopheles gambiae in Tanzania. Parasitology 102 Pt 2: 167-177.
112. Wu Y, Wang X, Liu X, Wang Y, (2003) Data-mining approaches reveal hidden families of proteases in the genome of malaria parasite. Genome Res 13: 601-616.
113. Kim R, Tanabe K, Uchida Y, Emi M, Inoue H, et al. (2002) Current status of the molecular mechanisms of anticancer drug-induced apoptosis. The contribution of molecular-level analysis to cancer chemotherapy. Cancer Chemother Pharmacol 50: 343-352.
114. Bhowmick IP, Kumar N, Sharma S, Isabelle Coppens I, Jarori GK, (2009) Plasmodium falciparum enolase: stage-specific expression and sub-cellular localization. Malar J 8: 179 doi:10.1186/1475-2875-8-179.