Plasmodium falciparum kelch 13: A potential molecular marker for tackling artemisinin-resistant malaria parasites

Expert Review of Anti-Infective Therapy

Volumn 14, Issue 1, 2016, Pages 125-135

  Mita, Toshihiro ^a   Tachibana, Shin Ichiro ^a   Hashimoto, Muneaki ^a   Hirai, Makoto ^a  

^a JUNTENDO UNIVERSITY SCHOOL OF MEDICINE   (Japan)

Author keywords

Artemisinin resistance; Kelch13; Phosphatidylinositol 3 kinase; Plasmodium; Ubiquitin proteasome system; Unfolded protein response pathway

Indexed keywords

ARTEMISININ; MOLECULAR MARKER; PHOSPHATIDYLINOSITOL 3 PHOSPHATE; PROTEASOME; UBIQUITIN; ANTIMALARIAL AGENT; ARTEMISININ DERIVATIVE; BIOLOGICAL MARKER; PHOSPHATIDYLINOSITOL 3 KINASE; PROTOZOAL PROTEIN; SIGNAL PEPTIDE;

ANTIMALARIAL DRUG RESISTANCE; DORMANCY; GENE; GENE MUTATION; GENETIC SIMILARITY; GENOME ANALYSIS; GROWTH INHIBITION; HUMAN; INTRACELLULAR SIGNALING; KELCH13 GENE; MEMBRANE DEPOLARIZATION; MONOTHERAPY; NONHUMAN; PARASITE CLEARANCE; PARASITE SURVIVAL; PLASMODIUM FALCIPARUM; POPULATION GENETICS; PREDICTIVE VALUE; REVIEW; SEQUENCE ANALYSIS; SINGLE NUCLEOTIDE POLYMORPHISM; SURVIVAL RATE; UNFOLDED PROTEIN RESPONSE; UPREGULATION; AFRICA SOUTH OF THE SAHARA; DRUG EFFECTS; DRUG RESISTANCE; GENE EXPRESSION REGULATION; GENETICS; MALARIA, FALCIPARUM; METABOLISM; PARASITOLOGY; SIGNAL TRANSDUCTION; SOUTHEAST ASIA;

AFRICA SOUTH OF THE SAHARA; ANTIMALARIALS; ARTEMISININS; ASIA, SOUTHEASTERN; BIOMARKERS; DRUG RESISTANCE; GENE EXPRESSION REGULATION; HUMANS; INTRACELLULAR SIGNALING PEPTIDES AND PROTEINS; MALARIA, FALCIPARUM; PHOSPHATIDYLINOSITOL 3-KINASE; PLASMODIUM FALCIPARUM; PROTEASOME ENDOPEPTIDASE COMPLEX; PROTOZOAN PROTEINS; SIGNAL TRANSDUCTION; UBIQUITIN; UNFOLDED PROTEIN RESPONSE;

EID: 84954383171     PISSN: 14787210     EISSN: 17448336     Source Type: Journal    
DOI: 10.1586/14787210.2016.1106938     Document Type: Review

References (107)

1. WHO. World malaria report 2014. Geneva: World Health Organization; 2014
2. Barnes KI, Durrheim DN, Little F, et al. Effect of artemether-lumefantrine policy and improved vector control on malaria burden in KwaZulu-Natal, South Africa. PLoS Med. 2005;2(11):e330
3. Enserink M. Combating malaria. Malaria treatment: ACT two. Science. 2007;318 (5850):560-563
4. Noedl H, Socheat D, Satimai W. Artemisinin-resistant malaria in Asia. N Engl J Med. 2009;361(5):540-541
5. Carrara VI, Zwang J, Ashley EA, et al. Changes in the treatment responses to artesunate-mefloquine on the northwestern border of Thailand during 13 years of continuous deployment. PLoS ONE. 2009;4(2):e4551
6. Dondorp AM, Nosten F, Yi P, et al. Artemisinin resistance in Plasmodium falciparum malaria. N Engl J Med. 2009;361(5):455-467
7. Amaratunga C, Sreng S, Suon S, et al. Artemisinin-resistant Plasmodium falciparum in Pursat province, western Cambodia: a parasite clearance rate study. Lancet Infect Dis. 2012;12(11):851-858
8. Ashley EA, Dhorda M, Fairhurst RM, et al. Spread of artemisinin resistance in Plasmodium falciparum malaria. N Engl J Med. 2014;371(5):411-423
9. Tun KM, Imwong M, Lwin KM, et al. Spread of artemisinin-resistant Plasmodium falciparum in Myanmar: a cross-sectional survey of the K13 molecular marker. Lancet Infect Dis. 2015;15 (4):415-421
10. Wootton JC, Feng X, Ferdig MT, et al. Genetic diversity and chloroquine selective sweeps in Plasmodium falciparum. Nature. 2002;418(6895):320-323
11. Roper C, Pearce R, Nair S, et al. Intercontinental spread of pyrimethamine-resistant malaria. Science. 2004;305 (5687):1124
12. McCollum AM, Poe AC, Hamel M, et al. Antifolate resistance in Plasmodium falciparum: multiple origins and identification of novel dhfr alleles. J Infect Dis. 2006;194(2):189-197
13. Maiga O, Djimde AA, Hubert V, et al. A shared Asian origin of the triplemutant dhfr allele in Plasmodium falciparum from sites across Africa. J Infect Dis. 2007;196(1):165-172
14. Mita T, Tanabe K, Takahashi N, et al. Indigenous evolution of Plasmodium falciparum pyrimethamine resistance multiple times in Africa. J Antimicrob Chemother. 2009;63(2):252-255
15. Mita T, Tanabe K, Kita K. Spread and evolution of Plasmodium falciparum drug resistance. Parasitol Int. 2009;58 (3):201-209
16. Mita T, Venkatesan M, Ohashi J, et al. Limited geographical origin and global spread of sulfadoxine-resistant dhps alleles in Plasmodium falciparum populations. J Infect Dis. 2011;204(12):1980-1988
17. Korenromp EL, Williams BG, Gouws E, et al. Measurement of trends in childhood malaria mortality in Africa: an assessment of progress toward targets based on verbal autopsy. Lancet Infect Dis. 2003;3 (6):349-358
18. Ariey F, Witkowski B, Amaratunga C, et al. A molecular marker of artemisininresistant Plasmodium falciparum malaria. Nature. 2014;505(7481):50-55
19. Cheeseman IH, McDew-White M, Phyo AP, et al. Pooled sequencing and rare variant association tests for identifying the determinants of emerging drug resistance in malaria parasites. Mol Biol Evol. 2015;32(4):1080-1090
20. Miotto O, Amato R, Ashley EA, et al. Genetic architecture of artemisinin-resistant Plasmodium falciparum. Nat Genet. 2015;47(3):226-234
21. White NJ. Qinghaosu (artemisinin): the price of success. Science. 2008;320 (5874):330-334
22. Dondorp AM, Yeung S, White L, et al. Artemisinin resistance: current status and scenarios for containment. Nat Rev Microbiol. 2010;8(4):272-280
23. Mita T, Tanabe K. Evolution of Plasmodium falciparum drug resistance: implications for the development and containment of artemisinin resistance. Jpn J Infect Dis. 2012;65(6):465-475
24. Wongsrichanalai C, Sibley CH. Fighting drug-resistant Plasmodium falciparum: the challenge of artemisinin resistance. Clin Microbiol Infect. 2013;19 (10):908-916
25. Trenholme CM, Williams RL, Desjardins RE, et al. Mefloquine (WR 142,490) in the treatment of human malaria. Science. 1975;190(4216):792-794
26. Cui L, Su XZ. Discovery, mechanisms of action and combination therapy of artemisinin. Expert Rev Anti Infect Ther. 2009;7(8):999-1013
27. Ashton M, Hai TN, Sy ND, et al. Artemisinin pharmacokinetics is timedependent during repeated oral administration in healthy male adults. Drug Metab Dispos. 1998;26(1):25-27
28. Teja-Isavadharm P, Nosten F, Kyle D, et al. Comparative bioavailability of oral, rectal, and intramuscular artemether in healthy subjects: use of simultaneous measurement by high performance liquid chromatography and bioassay. Br J Clin Pharmacol. 1996;42(5):599-604
29. Meshnick SR, Taylor TE, Kamchonwongpaisan S. Artemisinin and the antimalarial endoperoxides: from herbal remedy to targeted chemotherapy. Microbiol Rev. 1996;60(2):301-315
30. Woodrow CJ, Haynes RK, Krishna S. Artemisinins. Postgrad Med J. 2005;81 (952):71-78
31. Pukrittayakamee S, Chotivanich K, Chantra A, et al. Activities of artesunate and primaquine against asexual-and sexual-stage parasites in falciparum malaria. Antimicrob Agents Chemother. 2004;48 (4):1329-1334
32. Okell LC, Drakeley CJ, Ghani AC, et al. Reduction of transmission from malaria patients by artemisinin combination therapies: a pooled analysis of six randomized trials. Malar J. 2008;7:125
33. O'Neill PM, Barton VE, Ward SA. The molecular mechanism of action of artemisinin-the debate continues. Molecules. 2010;15(3):1705-1721
34. Ding XC, Beck HP, Raso G. Plasmodium sensitivity to artemisinins: magic bullets hit elusive targets. Trends Parasitol. 2011;27(2):73-81
35. Klonis N, Crespo-Ortiz MP, Bottova I, et al. Artemisinin activity against Plasmodium falciparum requires hemoglobin uptake and digestion. Proc Natl Acad Sci USA. 2011;108(28):11405-11410
36. Meshnick SR. Artemisinin: mechanisms of action, resistance and toxicity. Int J Parasitol. 2002;32(13):1655-1660
37. Wang J, Huang L, Li J, et al. Artemisinin directly targets malarial mitochondria through its specific mitochondrial activation. PLoS One. 2010;5(3):e9582
38. Haynes RK, Ho WY, Chan HW, et al. Highly antimalaria-active artemisinin derivatives: biological activity does not correlate with chemical reactivity. Angew Chem Int Edit. 2004;43(11):1381-1385
39. Lin JW, Spaccapelo R, Schwarzer E, et al. Replication of Plasmodium in reticulocytes can occur without hemozoin formation, resulting in chloroquine resistance. J Exp Med. 2015;212(6):893-903
40. Bommer U-A, Thiele B-J. The translationally controlled tumour protein (TCTP). Int J Biochem Cell Biol. 2004;36(3):379-385
41. Bhisutthibhan J, Pan X-Q, Hossler PA, et al. The Plasmodium falciparum translationally controlled tumor protein homolog and its reaction with the antimalarial drug artemisinin. J Biol Chem. 1998;273(26):16192-16198
42. Mathieu C, Demarta-Gatsi C, Porcherie A, et al. Plasmodium berghei histaminereleasing factor favours liver-stage development via inhibition of IL-6 production and associates with a severe outcome of disease. Cell Microbiol. 2015;17(4):542-558
43. Eckstein-Ludwig U, Webb R, Van Goethem I, et al. Artemisinins target the SERCA of Plasmodium falciparum. Nature. 2003;424(6951):957-961
44. Uhlemann AC, Cameron A, Eckstein-Ludwig U, et al. A single amino acid residue can determine the sensitivity of SERCAs to artemisinins. Nat Struct Mol Biol. 2005;12(7):628-629
45. Valderramos SG, Scanfeld D, Uhlemann AC, et al. Investigations into the role of the Plasmodium falciparum SERCA (PfATP6) L263E mutation in artemisinin action and resistance. Antimicrob Agents Chemother. 2010;54(9):3842-3852
46. Jambou R, Legrand E, Niang M, et al. Resistance of Plasmodium falciparum field isolates to in-vitro artemether and point mutations of the SERCA-type PfATPase6. Lancet. 2005;366 (9501):1960-1963
47. Ferreira ID, Martinelli A, Rodrigues LA, et al. Plasmodium falciparum from Para state (Brazil) shows satisfactory in vitro response to artemisinin derivatives and absence of the S769N mutation in the SERCA-type PfATPase6. Trop Med Int Health. 2008;13(2):199-207
48. Tahar R, Ringwald P, Basco LK. Molecular epidemiology of malaria in Cameroon. XXVIII. In vitro activity of dihydroartemisinin against clinical isolates of Plasmodium falciparum and sequence analysis of the P. falciparum ATPase 6 gene. Am J Trop Med Hyg. 2009;81 (1):13-18
49. Arnou B, Montigny C, Morth J, et al. The Plasmodium falciparum Ca2 +-ATPase PfATP6: insensitive to artemisinin, but a potential drug target. Biochem Soc Trans. 2011;39(3):823
50. Noedl H. Artemisinin resistance: how can we find it? Trends Parasitol. 2005;21 (9):404-405
51. WHO. Global report on antimalarial drug efficacy and drug resistance: 2000-2010. Geneva: World Health Organization; 2010
52. Witkowski B, Lelievre J, Barragan MJ, et al. Increased tolerance to artemisinin in Plasmodium falciparum is mediated by a quiescence mechanism. Antimicrob Agents Chemother. 2010;54(5):1872-1877
53. Saralamba S, Pan-Ngum W, Maude RJ, et al. Intrahost modeling of artemisinin resistance in Plasmodium falciparum. Proc Natl Acad Sci USA. 2011;108 (1):397-402
54. Witkowski B, Amaratunga C, Khim N, et al. Novel phenotypic assays for the detection of artemisinin-resistant Plasmodium falciparum malaria in Cambodia: in-vitro and ex-vivo drugresponse studies. Lancet Infect Dis. 2013;13(12):1043-1049
55. Cheng Q, Kyle DE, Gatton ML. Artemisinin resistance in Plasmodium falciparum: a process linked to dormancy? Int J Parasitol Drugs Drug Resist. 2012;2:249-255
56. Nguyen DS, Dao BH, Nguyen PD, et al. Treatment of malaria in Vietnam with oral artemisinin. Am J Trop Med Hyg. 1993;48(3):398-402
57. De Vries PJ, Dien TK. Clinical pharmacology and therapeutic potential of artemisinin and its derivatives in the treatment of malaria. Drugs. 1996;52 (6):818-836
58. Looareesuwan S, Wilairatana P, Viravan C, et al. Open randomized trial of oral artemether alone and a sequential combination with mefloquine for acute uncomplicated falciparum malaria. Am J Trop Med Hyg. 1997;56(6):613-617
59. Hoshen M, Na-Bangchang K, Stein W, et al. Mathematical modelling of the chemotherapy of Plasmodium falciparum malaria with artesunate: postulation of 'dormancy', a partial cytostatic effect of the drug, and its implication for treatment regimens. Parasitology. 2000;121 (03):237-246
60. Teuscher F, Gatton ML, Chen N, et al. Artemisinin-induced dormancy in plasmodium falciparum: duration, recovery rates, and implications in treatment failure. J Infect Dis. 2010;202(9):1362-1368
61. Teuscher F, Chen N, Kyle DE, et al. Phenotypic changes in artemisinin-resistant Plasmodium falciparum lines in vitro: evidence for decreased sensitivity to dormancy and growth inhibition. Antimicrob Agents Chemother. 2012;56 (1):428-431
62. Peatey CL, Chavchich M, Chen N, et al. Mitochondrial membrane potential in a small subset of artemisinin-induced dormant plasmodium falciparum parasites in vitro. J Infect Dis. 2015;212(3):426-434
63. Nakazawa S, Kanbara H, Aikawa M. Plasmodium falciparum: recrudescence of parasites in culture. Exp Parasitol. 1995;81(4):556-563
64. Nakazawa S, Maoka T, Uemura H, et al. Malaria parasites giving rise to recrudescence in vitro. Antimicrob Agents Chemother. 2002;46(4):958-965
65. Rittershaus ES, Baek SH, Sassetti CM. The normalcy of dormancy: common themes in microbial quiescence. Cell Host Microbe. 2013;13(6):643-651
66. Nosten F. Waking the sleeping beauty. J Infect Dis. 2010;202(9):1300-1301
67. Witkowski B, Khim N, Chim P, et al. Reduced artemisinin susceptibility of Plasmodium falciparum ring stages in western Cambodia. Antimicrob Agents Chemother. 2013;57(2):914-923
68. Chavchich M, Gerena L, Peters J, et al. Role of pfmdr1 amplification and expression in induction of resistance to artemisinin derivatives in Plasmodium falciparum. Antimicrob Agents Chemother. 2010;54(6):2455-2464
69. Cui L, Wang Z, Miao J, et al. Mechanisms of in vitro resistance to dihydroartemisinin in Plasmodium falciparum. Mol Microbiol. 2012;86(1):111-128
70. Cheeseman IH, Miller BA, Nair S, et al. A major genome region underlying artemisinin resistance in malaria. Science. 2012;336(6077):79-82
71. Takala-Harrison S, Clark TG, Jacob CG, et al. Genetic loci associated with delayed clearance of Plasmodium falciparum following artemisinin treatment in southeast Asia. Proc Natl Acad Sci USA. 2013;110 (1):240-245
72. Ghorbal M, Gorman M, Macpherson CR, et al. Genome editing in the human malaria parasite Plasmodium falciparum using the CRISPR-Cas9 system. Nat Biotechnol. 2014;32(8):819-821
73. Straimer J, Gnadig NF, Witkowski B, et al. Drug resistance. K13-propeller mutations confer artemisinin resistance in Plasmodium falciparum clinical isolates. Science. 2015;347(6220):428-431
74. Bardwell VJ, Treisman R. The POZ domain: a conserved protein-protein interaction motif. Genes Dev. 1994;8 (14):1664-1677
75. Zollman S, Godt D, Prive GG, et al. The Btb domain, found primarily in zinc-finger proteins, defines an evolutionarily conserved family that includes several developmentally-regulated genes in drosophila. Proc Natl Acad Sci USA. 1994;91(22):10717-10721
76. Adams J, Kelso R, Cooley L. The kelch repeat superfamily of proteins: propellers of cell function. Trends Cell Biol. 2000;10(1):17-24
77. Peterson DS, Walliker D, Wellems TE. Evidence that a point mutation in dihydrofolate reductase-thymidylate synthase confers resistance to pyrimethamine in falciparum malaria. Proc Natl Acad Sci USA. 1988;85(23):9114-9118
78. Fidock DA, Nomura T, Talley AK, et al. Mutations in the P. falciparum digestive vacuole transmembrane protein PfCRT and evidence for their role in chloroquine resistance. Mol Cell. 2000;6(4):861-871
79. Hawkes M, Conroy AL, Opoka RO, et al. Slow clearance of Plasmodium falciparum in severe pediatric malaria, Uganda, 2011-2013. Emerg Infect Dis. 2015;21 (7):1237-1239
80. Huang F, Takala-Harrison S, Jacob CG, et al. A single mutation in K13 predominates in southern China and is associated with delayed clearance of Plasmodium falciparum following artemisinin treatment. J Infect Dis. 2015. DOI:10.1093/ infdis/jiv249
81. Leang R, Taylor WR, Bouth DM, et al. Evidence of falciparum malaria multidrug resistance to artemisinin and piperaquine in western Cambodia: dihydroartemisinin-piperaquine open-label multicenter clinical assessment. Antimicrob Agents Chemother. 2015;59(8):4719-4726
82. Thriemer K, Hong NV, Rosanas-Urgell A, et al. Delayed parasite clearance after treatment with dihydroartemisinin-piperaquine in Plasmodium falciparum malaria patients in central Vietnam. Antimicrob Agents Chemother. 2014;58(12):7049-7055
83. Ouattara A, Kone A, Adams M, et al. Polymorphisms in the K13-propeller gene in artemisininsusceptible plasmodium falciparum parasites from Bougoula-Hameau and Bandiagara, Mali. Am J Trop Med Hyg. 2015;92(6):1202-1206
84. Plucinski MM, Talundzic E, Morton L, et al. Efficacy of artemether-lumefantrine and dihydroartemisinin-piperaquine for treatment of uncomplicated malaria in children in Zaire and Uige Provinces, Angola. Antimicrob Agents Chemother. 2015;59(1):437-443
85. Krishna S, Pulcini S, Moore CM, et al. Pumped up: reflections on PfATP6 as the target for artemisinins. Trends Pharmacol Sci. 2014;35(1):4-11
86. Mbengue A, Bhattacharjee S, Pandharkar T, et al. A molecular mechanism of artemisinin resistance in Plasmodium falciparum malaria. Nature. 2015;520 (7549):683-687
87. Davis WJ, Lehmann PZ, Li W. Nuclear PI3K signaling in cell growth and tumorigenesis. Front Cell Dev Biol. 2015;3:24
88. Ron D, Walter P. Signal integration in the endoplasmic reticulum unfolded protein response. Nat Rev Mol Cell Biol. 2007;8(7):519-529
89. Amm I, Sommer T, Wolf DH. Protein quality control and elimination of protein waste: the role of the ubiquitin-proteasome system. Biochim Biophys Acta. 2014;1843(1):182-196
90. Mok S, Imwong M, Mackinnon MJ, et al. Artemisinin resistance in Plasmodium falciparum is associated with an altered temporal pattern of transcription. BMC Genomics. 2011;12:391
91. Dogovski C, Xie SC, Burgio G, et al. Targeting the cell stress response of Plasmodium falciparum to overcome artemisinin resistance. PLoS Biol. 2015;13 (4):e1002132
92. Mok S, Ashley EA, Ferreira PE, et al. Drug resistance. Population transcriptomics of human malaria parasites reveals the mechanism of artemisinin resistance. Science. 2015;347(6220):431-435
93. Hetz C, Chevet E, Oakes SA. Proteostasis control by the unfolded protein response. Nat Cell Biol. 2015;17(7):829-838
94. Burrows J. Microbiology: malaria runs rings round artemisinin. Nature. 2015;520(7549):628-630
95. Tawk L, Chicanne G, Dubremetz JF, et al. Phosphatidylinositol 3-phosphate, an essential lipid in Plasmodium, localizes to the food vacuole membrane and the apicoplast. Eukaryot Cell. 2010;9 (10):1519-1530
96. Klonis N, Xie SC, McCaw JM, et al. Altered temporal response of malaria parasites determines differential sensitivity to artemisinin. Proc Natl Acad Sci USA. 2013;110(13):5157-5162
97. Abu Bakar N, Klonis N, Hanssen E, et al. Digestive-vacuole genesis and endocytic processes in the early intraerythrocytic stages of Plasmodium falciparum. J Cell Sci. 2010;123(Pt 3):441-450
98. Price RN, Cassar C, Brockman A, et al. The pfmdr1 gene is associated with a multidrug-resistant phenotype in Plasmodium falciparum from the western border of Thailand. Antimicrob Agents Chemother. 1999;43(12):2943-2949
99. Pickard AL, Wongsrichanalai C, Purfield A, et al. Resistance to antimalarials in southeast Asia and genetic polymorphisms in pfmdr1. Antimicrob Agents Chemother. 2003;47(8):2418-2423
100. Price RN, Uhlemann AC, Brockman A, et al. Mefloquine resistance in Plasmodium falciparum and increased pfmdr1 gene copy number. Lancet. 2004;364(9432):438-447
101. Sidhu ABS, Uhlemann A-C, Valderramos SG, et al. Decreasing pfmdr1 copy number in Plasmodium falciparum malaria heightens susceptibility to mefloquine, lumefantrine, halofantrine, quinine, and artemisinin. J Infect Dis. 2006;194 (4):528-535
102. Cooper RA, Ferdig MT, Su XZ, et al. 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. 2002;61(1):35-42
103. Sidhu AB, Verdier-Pinard D, Fidock DA. Chloroquine resistance in Plasmodium falciparum malaria parasites conferred by pfcrt mutations. Science. 2002;298 (5591):210-213
104. Hunt P, Afonso A, Creasey A, et al. Gene encoding a deubiquitinating enzyme is mutated in artesunate-and chloroquine-resistant rodent malaria parasites. Mol Microbiol. 2007;65 (1):27-40
105. Hunt P, Martinelli A, Modrzynska K, et al. Experimental evolution, genetic analysis and genome re-sequencing reveal the mutation conferring artemisinin resistance in an isogenic lineage of malaria parasites. BMC Genomics. 2010;11:499
106. Takala-Harrison S, Jacob CG, Arze C, et al. Independent emergence of artemisinin resistance mutations among plasmodium falciparum in southeast Asia. J Infect Dis. 2015;211(5):670-679
107. Miotto O, Almagro-Garcia J, Manske M, et al. Multiple populations of artemisininresistant Plasmodium falciparum in Cambodia. Nat Genet. 2013;45(6):648-655.