In vitro resistance to experimental antimalarials
Blasco B, Leroy D, Fidock DA. Antimalarial drug resistance: linking Plasmodium falciparum parasite biology to the clinic. Nat Med. 2017 23(8):917-928. PMID: 28777791.
Resistance gene(s) Annotation/Target Target location Pathway/mechanism Selection compound Parent strain log10 MIR IC50 increase Genetic changes Transcript
PF3D7_1211900
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PfATP4 Plasma membrane Ion homeostasis KAE609 Dd2 <8 (multiple strains) 2 to 33–fold >36 SNPs identified
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PF3D7_1211900
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PfATP4 Plasma membrane SJ557733 3D7, Dd2 7 (3D7) 3 to 480–fold L350H, P412T, V415D
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PF3D7_1211900
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PfATP4 Plasma membrane 21A092 Dd2 <9.5 (Dd2) 20–fold V178I
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PF3D7_1341900
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V-type proton ATPase subunit D pH regulation pH regulation AZ412 Dd2 <10 (Dd2) 3 to 6-fold G29V
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PF3D7_1451100
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eEF2 Protein synthesis Protein synthesis DDD107498 Dd2, 7G8, 3D7 6 (Dd2), 7(7G8, 3D7) 7 to 5,600–fold E134D, E134G and P754S/A, I183T and/or L755F, T185I and S474R, Y186N, S474R, A482T, L755F
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PF3D7_0622800
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leucine-tRNA ligase Protein synthesis Protein synthesis AN6426 Dd2 8 (Dd2) 1.5- to 60-fold T400I, V568L, E628G, V630L
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PF3D7_1332900
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isoleucine-tRNA ligase Protein synthesis Protein synthesis Thiaisoleucine 3D7 nd 2-fold L810F
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PF3D7_1213800
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prolyl-tRNA synthetase proline-tRNA ligase Protein synthesis Protein synthesis Halofuginone Dd2 nd 60- to 360-fold L482H/F
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PF3D7_1350100
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lysine-tRNA ligase Protein synthesis Protein synthesis Cladosporin Dd2 nd 6-fold Amplification of pfKrs1
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PF3D7_0109800
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phenylalanyl-tRNA synthetase alpha subunit Protein synthesis Protein synthesis BRD1095 and BRD7929 Dd2 BRD7929: >9 (Dd2) 4- to 84-fold M316I, L550V, G512E and V545I
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PF3D7_1438500
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cleavage and polyadenylation specificity factor subunit 3 mRNA processing mRNA processing AN3661 Dd2, W2 6 (Dd2) 11–to 200–fold H36Y, T406I, Y408S, T409A, D470N, amplification pfcpsf3
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PF3D7_0321900
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cyclic amine resistance locus protein Transporter of ER/Golgi membrane Mitochondrial transporter Transporter of ER/Golgi membrane Mitochondrial transporter KAF156 and analogues 3D7, Dd2 8 (Dd2) 6- to 890-fold PfCARL Q821H, P822T, E834D, S1076I/R, I1139K; PfUGT F37V; PfACT A94T, R108K, S110R, D165N, C193*, S242*, L253*, G559K
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PF3D7_1113300 UDP-galactose transporter, putative Transporter of ER/Golgi membrane Mitochondrial transporter Transporter of ER/Golgi membrane Mitochondrial transporter KAF156 and analogues 3D7, Dd2 8 (Dd2) 6- to 890-fold PfCARL Q821H, P822T, E834D, S1076I/R, I1139K; PfUGT F37V; PfACT A94T, R108K, S110R, D165N, C193*, S242*, L253*, G559K
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PF3D7_1036800 acetyl-CoA transporter, putative Transporter of ER/Golgi membrane Mitochondrial transporter KAF156 and analogues 3D7, Dd2 8 (Dd2) 6- to 890-fold PfCARL Q821H, P822T, E834D, S1076I/R, I1139K; PfUGT F37V; PfACT A94T, R108K, S110R, D165N, C193*, S242*, L253*, G559K
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PF3D7_0509800
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phosphatidylinositol 4-kinase Membrane trafficking Membrane trafficking KAI407 Dd2 nd 2- to 10-fold H1484Y, amplification of pfpi4k
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MMV390048 Dd2 6 (Dd2) 4- to 5–fold S743T, A1319V
mal_mito_3
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apocytochrome b (cyb) Electron transport Electron transport ELQ-300 Dd2 <8 (Dd2) 24-fold I22L
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Decoquinate 3D7 nd 90-fold A122T and Y126C
PF3D7_0603300
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dihydroorotate dehydrogenase Pyrimidine biosynthesis Pyrimidine biosynthesis DSM265 Dd2, K1 5.3 to 7.3 (Dd2), 8.3 (K1) 3- to 32-fold G181C, amplification of pfdhodh
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PF3D7_0523000
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multidrug resistance protein 1 ABC transporter B family member 1 PfMDR1* Unknown Unknown ATC451840 Dd2, 7G8, NF54 6 (Dd2), 7 (7G8 and NF54) 12- to 56-fold G316R, M841I, M841I and M924I, A807V/T, Y1076F
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PF3D7_API00100 apicoplast ribosomal protein S4 Protein synthesis Protein synthesis Azithromycin 7G8, Dd2, D10 nd 16- to 17-fold (7G8, Dd2); 57-fold (D10) G76V (7G8 and Dd2), G91D (D10)
PF3D7_1225100
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apicoplast isoleucine--tRNA ligase, Protein synthesis Protein synthesis Mupirocin 3D7, HB3 nd 10- to 18-fold P1233S
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PF3D7_1467300
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1-deoxy-D-xylulose 5-phosphate reductoisomerase Isoprenoid synthesis Isoprenoid synthesis Fosmidomycin Dd2 nd 8-fold Amplification of pfdxr
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MIR: Minimum inoculum of resistance; SNP: single nucleotide polymorphism; nd: not determined
* Whether this is the primary molecular target or the mechanism of resistance remains to be clarified.
More information about the selection compound can be found by entering into the particular gene
Online articles related to In vitro resistance to experimental antimalarials retrieved from PubMed