Drug resistance genomics of the antimalarial drug artemisinin

Genome Biology

Volumn 15, Issue 11, 2014, Pages

  Winzeler, Elizabeth A ^a   Manary, Micah J ^a  

^a UNIVERSITY OF CALIFORNIA   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ARTEMISININ; KELCH PROPELLER DOMAIN CONTAINING PROTEIN; UNCLASSIFIED DRUG; ANTIMALARIAL AGENT; ARTEMISININ DERIVATIVE;

ANTIMALARIAL DRUG RESISTANCE; DNA MODIFICATION; DRUG TOLERANCE; EVOLUTION; GENE; GENE EXPRESSION; GENE MUTATION; GENOMICS; HUMAN; MALARIA FALCIPARUM; MICROARRAY ANALYSIS; MONOTHERAPY; NEXT GENERATION SEQUENCING; NONHUMAN; PARASITE CLEARANCE; PFATP6 GENE; PFCRT GENE; PFKELCH13 GENE; PFMDR1 GENE; PFUBP1 GENE; PLASMODIUM FALCIPARUM; POLYMERASE CHAIN REACTION; REVIEW; SANGER SEQUENCING; SEQUENCE ANALYSIS; SINGLE NUCLEOTIDE POLYMORPHISM; DRUG EFFECTS; DRUG RESISTANCE; GENETICS; MALARIA, FALCIPARUM; PARASITOLOGY;

PLASMODIUM FALCIPARUM;

ANTIMALARIALS; ARTEMISININS; DRUG RESISTANCE; GENOMICS; HUMANS; MALARIA, FALCIPARUM; PLASMODIUM FALCIPARUM;

EID: 84924527760     PISSN: 14747596     EISSN: 1474760X     Source Type: Journal    
DOI: 10.1186/s13059-014-0544-6     Document Type: Review

References (83)

1. Murray CJ, Ortblad KF, Guinovart C, Lim SS, Wolock TM, Roberts DA, Dansereau EA, Graetz N, Barber RM, Brown JC, Wang H, Duber HC, Naghavi M, Dicker D, Dandona L, Salomon JA, Heuton KR, Foreman K, Phillips DE, Fleming TD, Flaxman AD, Phillips BK, Johnson EK, Coggeshall MS, Abd-Allah F, Abera SF, Abraham JP, Abubakar I, Abu-Raddad LJ, Abu-Rmeileh NM, et al: Global, regional, and national incidence and mortality for HIV, tuberculosis, and malaria during 1990-2013: a systematic analysis for the Global Burden of Disease Study 2013. Lancet 2014, 384:1005-1070.
2. World Health Organization: World malaria report 2013. Geneva: WHO; 2013.
3. Carter R, Mendis KN: Evolutionary and historical aspects of the burden of malaria. Clin Microbiol Rev 2002, 15:564-594.
4. Looareesuwan S, Viravan C, Webster HK, Kyle DE, Hutchinson DB, Canfield CJ: Clinical studies of atovaquone, alone or in combination with other antimalarial drugs, for treatment of acute uncomplicated malaria in Thailand. Am J Trop Med Hyg 1996, 54:62-66.
5. Miller LH, Su X: Artemisinin: discovery from the Chinese herbal garden. Cell 2011, 146:855-858.
6. Sherman IW: Magic Bullets to Conquer Malaria: from Quinine to Qinghaosu. ASM Press; 2011.
7. Saunders DL, Vanachayangkul P, Lon C: Dihydroartemisinin-piperaquine failure in Cambodia. New Engl J Med 2014, 371:484-485.
8. White NJ, Pukrittayakamee S, Phyo AP, Rueangweerayut R, Nosten F, Jittamala P, Jeeyapant A, Jain JP, Lefevre G, Li R, Magnusson B, Diagana TT, Leong FJ: Spiroindolone KAE609 for falciparum and vivax malaria. N Engl J Med 2014, 371:403-410.
9. Leong FJ, Zhao R, Zeng S, Magnusson B, Diagana TT, Pertel P: A first-in-human randomized, double-blind, placebo-controlled, single- and multiple-ascending oral dose study of novel imidazolopiperazine KAF156 to assess its aafety, tolerability, and pharmacokinetics in healthy adult volunteers. Antimicrob Agents Chemother 2014, 58:6437-6443.
10. Leong FJ, Li R, Jain JP, Lefèvre G, Magnusson B, Diagana TT, Pertel P: A first-in-human randomized, double-blind, placebo-controlled, single-and multiple-ascending oral dose study of novel antimalarial spiroindolone KAE609 (cipargamin), to assess the safety, tolerability and pharmacokinetics in healthy adult volunteers. Antimicrob Agents Chemother 2014, 58:6209-6214.
11. Eastman RT, Fidock DA: Artemisinin-based combination therapies: a vital tool in efforts to eliminate malaria. Nat Rev Microbiol 2009, 7:864-874.
12. Eckstein-Ludwig U, Webb RJ, Van Goethem ID, East JM, Lee AG, Kimura M, O'Neill PM, Bray PG, Ward SA, Krishna S: Artemisinins target the SERCA of Plasmodium falciparum . Nature 2003, 424:957-961.
13. Valderramos SG, Scanfeld D, Uhlemann A-C, Fidock DA, Krishna S: Investigations into the role of the Plasmodium falciparum SERCA (PfATP6) L263E mutation in artemisinin action and resistance. Antimicrob Agents Chemother 2010, 54:3842-3852.
14. Cardi D, Pozza A, Arnou B, Marchal E, Clausen JD, Andersen JP, Krishna S, Møller JV, le Maire M, Jaxel C: Purified E255L mutant SERCA1a and purified PfATP6 are sensitive to SERCA-type inhibitors but insensitive to artemisinins. J Biol Chem 2010, 285:26406-26416.
15. 2+ -ATPase PfATP6: insensitive to artemisinin, but a potential drug target. Biochem Soc Trans 2011, 39:823.
16. 2+ ATPase), tctp, mdr1, and cg10. Antimicrob Agents Chemother 2006, 50:480-489.
17. Dondorp AM, Nosten F, Yi P, Das D, Phyo AP, Tarning J, Lwin KM, Ariey F, Hanpithakpong W, Lee SJ, Ringwald P, Silamut K, Imwong M, Chotivanich K, Lim P, Herdman T, An SS, Yeung S, Singhasivanon P, Day NP, Lindegardh N, Socheat D, White NJ: Artemisinin resistance in Plasmodium falciparum malaria. N Engl J Med 2009, 361:455-467.
18. Wilson CM, Serrano AE, Wasley A, Bogenschutz MP, Shankar AH, Wirth DF: Amplification of a gene related to mammalian mdr genes in drug-resistant Plasmodium falciparum . Science 1989, 244:1184-1186.
19. Foote SJ, Thompson JK, Cowman AF, Kemp DJ: Amplification of the multidrug resistance gene in some chloroquine-resistant isolates of P. falciparum . Cell 1989, 57:921-930.
20. Sidhu AB, Verdier-Pinard D, Fidock DA: Chloroquine resistance in Plasmodium falciparum malaria parasites conferred by pfcrt mutations. Science 2002, 298:210-213.
21. Sidhu AB, Uhlemann AC, Valderramos SG, Valderramos JC, Krishna S, Fidock DA: Decreasing pfmdr1 copy number in Plasmodium falciparum malaria heightens susceptibility to mefloquine, lumefantrine, halofantrine, quinine, and artemisinin. J Infect Dis 2006, 194:528-535.
22. Sidhu AB, Valderramos SG, Fidock DA: pfmdr1 mutations contribute to quinine resistance and enhance mefloquine and artemisinin sensitivity in Plasmodium falciparum . Mol Microbiol 2005, 57:913-926.
23. Dahlstrom S, Ferreira PE, Veiga MI, Sedighi N, Wiklund L, Martensson A, Farnert A, Sisowath C, Osorio L, Darban H, Andersson B, Kaneko A, Conseil G, Björkman A, Gil JP: Plasmodium falciparum multidrug resistance protein 1 and artemisinin-based combination therapy in Africa. J Infect Dis 2009, 200:1456-1464.
24. Sisowath C, Petersen I, Veiga MI, Martensson A, Premji Z, Bjorkman A, Fidock DA, Gil JP: In vivo selection of Plasmodium falciparum parasites carrying the chloroquine-susceptible pfcrt K76 allele after treatment with artemether-lumefantrine in Africa. J Infect Dis 2009, 199:750-757.
25. Ecker A, Lehane AM, Clain J, Fidock DA: PfCRT and its role in antimalarial drug resistance. Trends Parasitol 2012, 28:504-514.
26. Imwong M, Dondorp AM, Nosten F, Yi P, Mungthin M, Hanchana S, Das D, Phyo AP, Lwin KM, Pukrittayakamee S, Lee SJ, Saisung S, Koecharoen K, Nguon C, Day NP, Socheat D, White NJ: Exploring the contribution of candidate genes to artemisinin resistance in Plasmodium falciparum . Antimicrob Agents Chemother 2010, 54:2886-2892.
27. Hunt P, Afonso A, Creasey A, Culleton R, Sidhu AB, Logan J, Valderramos SG, McNae I, Cheesman S, do Rosario V, Carter R, Fidock DA, Cravo P: Gene encoding a deubiquitinating enzyme is mutated in artesunate- and chloroquine-resistant rodent malaria parasites. Mol Microbiol 2007, 65:27-40.
28. Martinelli A, Cheesman S, Hunt P, Culleton R, Raza A, Mackinnon M, Carter R: A genetic approach to the de novo identification of targets of strain-specific immunity in malaria parasites. Proc Natl Acad Sci U S A 2005, 102:814-819.
29. Henriques G, Hallett RL, Beshir KB, Gadalla NB, Johnson RE, Burrow R, van Schalkwyk DA, Sawa P, Omar SA, Clark TG, Bousema T, Sutherland CJ: Directional selection at the pfmdr1, pfcrt, pfubp1, and pfap2mu loci of Plasmodium falciparum in Kenyan children treated with ACT. J Infect Dis 2014, Epub ahead of print.
30. Dharia NV, Sidhu AB, Cassera MB, Westenberger SJ, Bopp SE, Eastman RT, Plouffe D, Batalov S, Park DJ, Volkman SK, Wirth DF, Zhou Y, Fidock DA, Winzeler EA: Use of high-density tiling microarrays to identify mutations globally and elucidate mechanisms of drug resistance in Plasmodium falciparum . Genome Biol 2009, 10:R21.
31. Rottmann M, McNamara C, Yeung BK, Lee MC, Zou B, Russell B, Seitz P, Plouffe DM, Dharia NV, Tan J, Cohen SB, Spencer KR, González-Páez GE, Lakshminarayana SB, Goh A, Suwanarusk R, Jegla T, Schmitt EK, Beck HP, Brun R, Nosten F, Renia L, Dartois V, Keller TH, Fidock DA, Winzeler EA, Diagana TT: Spiroindolones, a potent compound class for the treatment of malaria. Science 2010, 329:1175-1180.
32. Meister S, Plouffe DM, Kuhen KL, Bonamy GM, Wu T, Barnes SW, Bopp SE, Borboa R, Bright AT, Che J, Cohen S, Dharia NV, Gagaring K, Gettayacamin M, Gordon P, Groessl T, Kato N, Lee MC, McNamara CW, Fidock DA, Nagle A, Nam TG, Richmond W, Roland J, Rottmann M, Zhou B, Froissard P, Glynne RJ, Mazier D, Sattabongkot J, et al: Imaging of Plasmodium liver stages to drive next-generation antimalarial drug discovery. Science 2011, 334:1372-1377.
33. Guler JL, Freeman DL, Ahyong V, Patrapuvich R, White J, Gujjar R, Phillips MA, DeRisi J, Rathod PK: Asexual populations of the human malaria parasite, Plasmodium falciparum , use a two-step genomic strategy to acquire accurate, beneficial DNA amplifications. PLoS Pathog 2013, 9:e1003375.
34. Tucker MS, Mutka T, Patel J, Kyle DE: Phenotypic and genotypic analysis of in vitro -selected artemisinin-resistant progeny of Plasmodium falciparum . Antimicrob Agents Chemother 2012, 56:302-314.
35. Tucker MS: Phenotypic and Genotypic Analysis of In Vitro Selected Artemisinin Resistant Plasmodium falciparum. University of South Florida, Global Health; 2010.
36. Ariey F, Witkowski B, Amaratunga C, Beghain J, Langlois AC, Khim N, Kim S, Duru V, Bouchier C, Ma L, Lim P, Leang R, Duong S, Sreng S, Suon S, Chuor CM, Bout DM, Ménard S, Rogers WO, Genton B, Fandeur T, Miotto O, Ringwald P, Le Bras J, Berry A, Barale JC, Fairhurst RM, Benoit-Vical F, Mercereau-Puijalon O, Ménard D: A molecular marker of artemisinin-resistant Plasmodium falciparum malaria. Nature 2014, 505:50-55.
37. Cui L, Wang Z, Miao J, Miao M, Chandra R, Jiang H, Su XZ, Cui L: Mechanisms of in vitro resistance to dihydroartemisinin in Plasmodium falciparum . Mol Microbiol 2012, 86:111-128.
38. Noedl H, Se Y, Schaecher K, Smith BL, Socheat D, Fukuda MM: Evidence of artemisinin-resistant malaria in western Cambodia. N Engl J Med 2008, 359:2619-2620.
39. Krishna S, Kremsner PG: Antidogmatic approaches to artemisinin resistance: reappraisal as treatment failure with artemisinin combination therapy. Trends Parasitol 2013, 29:313-317.
40. Ferreira PE, Culleton R, Gil JP, Meshnick SR: Artemisinin resistance in Plasmodium falciparum: what is it really? Trends Parasitol 2013, 29:318-320.
41. Dondorp AM, Ringwald P: Artemisinin resistance is a clear and present danger. Trends Parasitol 2013, 29:359-360.
42. Amaratunga C, Sreng S, Suon S, Phelps ES, Stepniewska K, Lim P, Zhou C, Mao S, Anderson JM, Lindegardh N, Jiang H, Song J, Su XZ, White NJ, Dondorp AM, Anderson TJ, Fay MP, Mu J, Duong S, Fairhurst RM: Artemisinin-resistan Plasmodium falciparum in Pursat province, western Cambodia: a parasite clearance rate study. Lancet Infect Dis 2012, 12:851-858.
43. Phyo AP, Nkhoma S, Stepniewska K, Ashley EA, Nair S, McGready R, ler Moo C, Al-Saai S, Dondorp AM, Lwin KM, Singhasivanon P, Day NP, White NJ, Anderson TJ, Nosten F: Emergence of artemisinin-resistant malaria on the western border of Thailand: a longitudinal study. Lancet 2012, 379:1960-1966.
44. Kyaw MP, Nyunt MH, Chit K, Aye MM, Aye KH, Aye MM, Lindegardh N, Tarning J, Imwong M, Jacob CG, Rasmussen C, Perin J, Ringwald P, Nyunt MM: Reduced susceptibility of Plasmodium falciparum to artesunate in southern Myanmar. PLoS One 2013, 8:e57689.
45. Anderson TJ, Nair S, Nkhoma S, Williams JT, Imwong M, Yi P, Socheat D, Das D, Chotivanich K, Day NP, White NJ, Dondorp AM: High heritability of malaria parasite clearance rate indicates a genetic basis for artemisinin resistance in western Cambodia. J Infect Dis 2010, 201:1326-1330.
46. Wootton JC, Feng X, Ferdig MT, Cooper RA, Mu J, Baruch DI, Magill AJ, Su XZ: Genetic diversity and chloroquine selective sweeps in Plasmodium falciparum . Nature 2002, 418:320-323.
47. Roper C, Pearce R, Nair S, Sharp B, Nosten F, Anderson T: Intercontinental spread of pyrimethamine-resistant malaria. Science 2004, 305:1124.
48. Yuan J, Cheng KC, Johnson RL, Huang R, Pattaradilokrat S, Liu A, Guha R, Fidock DA, Inglese J, Wellems TE, Austin CP, Su XZ: Chemical genomic profiling for antimalarial therapies, response signatures, and molecular targets. Science 2011, 333:724-729.
49. Mu J, Myers RA, Jiang H, Liu S, Ricklefs S, Waisberg M, Chotivanich K, Wilairatana P, Krudsood S, White NJ, Udomsangpetch R, Cui L, Ho M, Ou F, Li H, Song J, Li G, Wang X, Seila S, Sokunthea S, Socheat D, Sturdevant DE, Porcella SF, Fairhurst RM, Wellems TE, Awadalla P, Su XZ: Plasmodium falciparum genome-wide scans for positive selection, recombination hot spots and resistance to antimalarial drugs. Nat Genet 2010, 42:268-271.
50. Park DJ, Lukens AK, Neafsey DE, Schaffner SF, Chang H-H, Valim C, Ribacke U, Van Tyne D, Galinsky K, Galligan M, Becker JS, Ndiaye D, Mboup S, Wiegand RC, Hartl DL, Sabeti PC, Wirth DF, Volkman SK: Sequence-based association and selection scans identify drug resistance loci in the Plasmodium falciparum malaria parasite. Proc Natl Acad Sci U S A 2012, 109:13052-13057.
51. Witkowski B, Amaratunga C, Khim N, Sreng S, Chim P, Kim S, Lim P, Mao S, Sopha C, Sam B, Anderson JM, Duong S, Chuor CM, Taylor WR, Suon S, Mercereau-Puijalon O, Fairhurst RM, Menard D: Novel phenotypic assays for the detection of artemisinin-resistant Plasmodium falciparum malaria in Cambodia: in-vitro and ex-vivo drug-response studies. Lancet Infect Dis 2013, 13:1043-1049.
52. Cheeseman IH, Miller BA, Nair S, Nkhoma S, Tan A, Tan JC, Al Saai S, Phyo AP, Moo CL, Lwin KM, McGready R, Ashley E, Imwong M, Stepniewska K, Yi P, Dondorp AM, Mayxay M, Newton PN, White NJ, Nosten F, Ferdig MT, Anderson TJ: A major genome region underlying artemisinin resistance in malaria. Science 2012, 336:79-82.
53. Takala-Harrison S, Clark TG, Jacob CG, Cummings MP, Miotto O, Dondorp AM, Fukuda MM, Nosten F, Noedl H, Imwong M, Bethell D, Se Y, Lon C, Tyner SD, Saunders DL, Socheat D, Ariey F, Phyo AP, Starzengruber P, Fuehrer HP, Swoboda P, Stepniewska K, Flegg J, Arze C, Cerqueira GC, Silva JC, Ricklefs SM, Porcella SF, Stephens RM, Adams M, et al: Genetic loci associated with delayed clearance of Plasmodium falciparum following artemisinin treatment in Southeast Asia. Proc Natl Acad Sci U S A 2013, 110:240-245.
54. Flegg JA, Guerin PJ, White NJ, Stepniewska K: Standardizing the measurement of parasite clearance in falciparum malaria: the parasite clearance estimator. Malar J 2011, 10:339.
55. Miotto O, Almagro-Garcia J, Manske M, Macinnis B, Campino S, Rockett KA, Amaratunga C, Lim P, Suon S, Sreng S, Anderson JM, Duong S, Nguon C, Chuor CM, Saunders D, Se Y, Lon C, Fukuda MM, Amenga-Etego L, Hodgson AV, Asoala V, Imwong M, Takala-Harrison S, Nosten F, Su XZ, Ringwald P, Ariey F, Dolecek C, Hien TT, Boni MF, et al: Multiple populations of artemisinin-resistant Plasmodium falciparum in Cambodia. Nat Genet 2013, 45:648-655.
56. Ashley EA, Dhorda M, Fairhurst RM, Amaratunga C, Lim P, Suon S, Sreng S, Anderson JM, Mao S, Sam B, Sopha C, Chuor CM, Nguon C, Sovannaroth S, Pukrittayakamee S, Jittamala P, Chotivanich K, Chutasmit K, Suchatsoonthorn C, Runcharoen R, Hien TT, Thuy-Nhien NT, Thanh NV, Phu NH, Htut Y, Han KT, Aye KH, Mokuolu OA, Olaosebikan RR, Folaranmi OO, et al: Spread of artemisinin resistance in Plasmodium falciparum malaria. N Engl J Med 2014, 371:411-423.
57. Leang R, Barrette A, Bouth DM, Menard D, Abdur R, Duong S, Ringwald P: Efficacy of dihydroartemisinin-piperaquine for treatment of uncomplicated Plasmodium falciparum and Plasmodium vivax in Cambodia, 2008 to 2010. Antimicrob Agents Chemother 2013, 57:818-826.
58. Jinek M, Chylinski K, Fonfara I, Hauer M, Doudna JA, Charpentier E: A programmable dual-RNA-guided DNA endonuclease in adaptive bacterial immunity. Science 2012, 337:816-821.
59. Wagner JC, Platt RJ, Goldfless SJ, Zhang F, Niles JC: Efficient CRISPR-Cas9-mediated genome editing in Plasmodium falciparum . Nat Methods 2014, 11:915-918.
60. Ghorbal M, Gorman M, Macpherson CR, Martins RM, Scherf A, Lopez-Rubio JJ: Genome editing in the human malaria parasite Plasmodium falciparum using the CRISPR-Cas9 system. Nat Biotechnol 2014, 32:819-821.
61. Conrad MD, Bigira V, Kapisi J, Muhindo M, Kamya MR, Havlir DV, Dorsey G, Rosenthal PJ: Polymorphisms in K13 and Falcipain-2 associated with artemisinin resistance are not prevalent in Plasmodium falciparum isolated from Ugandan children. PLoS One 2014, 9:e105690.
62. Taylor SM, Parobek CM, DeConti DK, Kayentao K, Coulibaly SO, Greenwood BM, Tagbor H, Williams J, Bojang K, Njie F, Desai M, Kariuki S, Gutman J, Mathanga DP, Mårtensson A, Ngasala B, Conrad MD, Rosenthal PJ, Tshefu AK, Moormann AM, Vulule JM, Doumbo OK, Ter Kuile FO, Meshnick SR, Bailey JA, Juliano JJ: Absence of putative Plasmodium falciparum artemisinin resistance mutations in sub-Saharan Africa: a molecular epidemiologic study. J Infect Dis 2014, Epub ahead of print.
63. Lopera-Mesa TM, Doumbia S, Chiang S, Zeituni AE, Konate DS, Doumbouya M, Keita AS, Stepniewska K, Traore K, Diakite SA, Ndiaye D, Sa JM, Anderson JM, Fay MP, Long CA, Diakite M, Fairhurst RM: Plasmodium falciparum clearance rates in response to artesunate in Malian children with malaria: effect of acquired immunity. J Infect Dis 2013, 207:1655-1663.
64. Ndour PA, Lopera-Mesa TM, Diakite SA, Chiang S, Mouri O, Roussel C, Jaureguiberry S, Biligui S, Kendjo E, Claessens A, Ciceron L, Mazier D, Thellier M, Diakité M, Fairhurst RM, Buffet PA: Plasmodium falciparum clearance is rapid and pitting independent in immune Malian children treated with artesunate for malaria. J Infect Dis 2014, Epub ahead of print.
65. World Health Organization: Global Plan for Artemisinin Resistance Containment (GPARC). Geneva; 2011.
66. Moehrle JJ, Duparc S, Siethoff C, van Giersbergen PL, Craft JC, Arbe-Barnes S, Charman SA, Gutierrez M, Wittlin S, Vennerstrom JL: First-in-man safety and pharmacokinetics of synthetic ozonide OZ439 demonstrates an improved exposure profile relative to other peroxide antimalarials. Br J Clin Pharmacol 2013, 75:524-537.
67. Klonis N, Xie SC, McCaw JM, Crespo-Ortiz MP, Zaloumis SG, Simpson JA, Tilley L: Altered temporal response of malaria parasites determines differential sensitivity to artemisinin. Proc Natl Acad Sci U S A 2013, 110:5157-5162.
68. Klonis N, Crespo-Ortiz MP, Bottova I, Abu-Bakar N, Kenny S, Rosenthal PJ, Tilley L: Artemisinin activity against Plasmodium falciparum requires hemoglobin uptake and digestion. Proc Natl Acad Sci U S A 2011, 108:11405-11410.
69. Smith Gueye C, Newby G, Hwang J, Phillips AA, Whittaker M, MacArthur JR, Gosling RD, Feachem RG: The challenge of artemisinin resistance can only be met by eliminating Plasmodium falciparum malaria across the Greater Mekong subregion. Malar J 2014, 13:286.
70. Walliker D, Quakyi IA, Wellems TE, McCutchan TF, Szarfman A, London WT, Corcoran LM, Burkot TR, Carter R: Genetic analysis of the human malaria parasite Plasmodium falciparum . Science 1987, 236:1661-1666.
71. Wellems TE, Walker-Jonah A, Panton LJ: Genetic mapping of the chloroquine-resistance locus on Plasmodium falciparum chromosome 7. Proc Natl Acad Sci U S A 1991, 88:3382-3386.
72. Gardner MJ, Hall N, Fung E, White O, Berriman M, Hyman RW, Carlton JM, Pain A, Nelson KE, Bowman S, Paulsen IT, James K, Eisen JA, Rutherford K, Salzberg SL, Craig A, Kyes S, Chan MS, Nene V, Shallom SJ, Suh B, Peterson J, Angiuoli S, Pertea M, Allen J, Selengut J, Haft D, Mather MW, Vaidya AB, Martin DM, et al: Genome sequence of the human malaria parasite Plasmodium falciparum . Nature 2002, 419:498-511.
73. Bopp SER, Manary MJ, Bright AT, Johnston GL, Dharia NV, Luna FL, McCormack S, Plouffe D, McNamara CW, Walker JR, Fidock DA, Denchi EL, Winzeler EA: Mitotic evolution of Plasmodium falciparum shows a stable core genome but recombination in antigen families. PLoS Genet 2013, 9:e1003293.
74. Vennerstrom JL, Arbe-Barnes S, Brun R, Charman SA, Chiu FC, Chollet J, Dong Y, Dorn A, Hunziker D, Matile H, McIntosh K, Padmanilayam M, Santo Tomas J, Scheurer C, Scorneaux B, Tang Y, Urwyler H, Wittlin S, Charman WN: Identification of an antimalarial synthetic trioxolane drug development candidate. Nature 2004, 430:900-904.
75. Klonis N, Creek DJ, Tilley L: Iron and heme metabolism in Plasmodium falciparum and the mechanism of action of artemisinins. Curr Opin Microbiol 2013, 16:722-727.
76. Delves M, Plouffe D, Scheurer C, Meister S, Wittlin S, Winzeler EA, Sinden RE, Leroy D: The activities of current antimalarial drugs on the life cycle stages of Plasmodium: a comparative study with human and rodent parasites. PLoS Med 2012, 9:e1001169.
77. World Health Organization: Guidelines for the Treatment of Malaria. 2nd edition. Geneva; 2010.
78. Steward R, Nusslein-Volhard C: The genetics of the dorsal-Bicaudal-D region of Drosophila melanogaster . Genetics 1986, 113:665-678.
79. Ma Q: Role of nrf2 in oxidative stress and toxicity. Ann Rev Pharmacol Toxicol 2013, 53:401-426.
80. Keum YS, Choi BY: Molecular and chemical regulation of the Keap1-Nrf2 signaling pathway. Molecules 2014, 19:10074-10089.
81. Hu M, Zou Y, Nambiar SM, Lee J, Yang Y, Dai G: Keap1 modulates the redox cycle and hepatocyte cell cycle in regenerating liver. Cell Cycle 2014, 13.
82. Witkowski B, Lelievre J, Barragan MJ, Laurent V, Su XZ, Berry A, Benoit-Vical F: Increased tolerance to artemisinin in Plasmodium falciparum is mediated by a quiescence mechanism. Antimicrob Agents Chemother 2010, 54:1872-1877.
83. Mok S, Imwong M, Mackinnon MJ, Sim J, Ramadoss R, Yi P, Mayxay M, Chotivanich K, Liong KY, Russell B, Socheat D, Newton PN, Day NP, White NJ, Preiser PR, Nosten F, Dondorp AM, Bozdech Z: Artemisinin resistance in Plasmodium falciparum is associated with an altered temporal pattern of transcription. BMC Genomics 2011, 12:391.