Resistance to experimental antimalarials generated in vitro
Blasco B, Leroy D, Fidock DA. Antimalarial drug resistance: linking Plasmodium falciparum parasite biology to the clinic. Nat Med. 2017 Aug 4;23(8):917-928. PMID: 28777791
Resistance gene(s) Annotation Target location Pathway/mechanism Target molecule Selection compound Parent strain IC50 increase Genetic changes
PFL0590c
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Image left : 8px, top : 12px
non-SERCA-type Ca2+ -transporting P-ATPase Plasma membrane Ion homeostasis PfATP4 KAE609 Dd2 2 to 33–fold >36 SNPs identified
SJ557733 3D7, Dd2 3 to 480–fold L350H, P412T, V415D
21A092 Dd2 20–fold V178I
PF13_0227
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V-type proton ATPase subunit D pH regulation V-type H+-ATPase AZ412 Dd2 3 to 6-fold G29V
PF14_0486
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Image left : 8px, top : 26px
elongation factor 2 Cytoplasm Protein synthesis eEF2 DDD107498 Dd2, 7G8, 3D7 7 to 5,600–fold E134D, E134G and P754S/A, I183T and/or L755F, T185I and S474R, Y186N, S474R, A482T, L755F
PFF1095w
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Image left : 8px, top : 26px
leucine--tRNA ligase Cytoplasm Protein synthesis LeuRS AN6426 Dd2 1.5- to 60-fold T400I, V568L, E628G, V630L
PF13_0179
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Image left : 8px, top : 26px
isoleucine-tRNA ligase Cytoplasm Protein synthesis Cyto-IleRS Thiaisoleucine 3D7 2-fold L810F
PFL0670c
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Image left : 8px, top : 26px
prolyl-tRNA synthetase proline--tRNA ligase Cytoplasm Protein synthesis ProRS Halofuginone Dd2 60- to 360-fold L482H/F
PF13_0262
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lysine-tRNA ligase Cytoplasm Protein synthesis LysRS Cladosporin Dd2 6-fold Amplification of pfKrs1
PFA0480w
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Image left : 8px, top : 26px
phenylalanyl-tRNA synthetase alpha subunit Cytoplasm Protein synthesis PheRS BRD1095 and BRD7929 Dd2 4- to 84-fold M316I, L550V, G512E and V545I
PF14_0364
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cleavage and polyadenylation specificity factor subunit 3 Nucleus mRNA processing CPSF3 AN3661 Dd2, W2 11–to 200–fold H36Y, T406I, Y408S, T409A, D470N, amplification pfcpsf3
PFC0970w
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Image left : 8px, top : 26px
cyclic amine resistance locus protein Endoplasmic reticulum and Golgi apparatus Unknown Unknown KAF156 and analogues 3D7, Dd2 6- to 890-fold Q821H, P822T, E834D, S1076I/R, I1139K
PF11_0141 UDP-galactose transporter Endoplasmic reticulum and Golgi apparatus transporter of ER membrane Unknown KAF156 and analogues 3D7, Dd2 6- to 890-fold F37V
PF10_0360 acetyl-CoA transporter Endoplasmic reticulum and Golgi apparatus Acetyl-CoA production in the mitochondrion Unknown KAF156 and analogues 3D7, Dd2 6- to 890-fold A94T, R108K, S110R, D165N, C193*, S242*, L253*, G559K
PFE0485w
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Image left : 8px, top : 26px
phosphatidylinositol 4-kinase Endomembrane system Membrane trafficking PI4K KAI407 Dd2 2- to 10-fold H1484Y, amplification of pfpi4k
PFE0485w
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Image left : 8px, top : 26px
phosphatidylinositol 4-kinase MMV390048 Dd2 4- to 5–fold S743T, A1319V
mal_mito_3
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apocytochrome b (cyb) Mitochondrion Electron transport CYTb ELQ-300 Dd2 24-fold I22L
apocytochrome b (cyb) Decoquinate 3D7 90-fold A122T and Y126C
PFF0160c
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Image left : 8px, top : 40px
dihydroorotate dehydrogenase Pyrimidine biosynthesis DHODH DSM265 Dd2, K1 3- to 32-fold G181C, amplification of pfdhodh
PFE1150w
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Image left : 8px, top : 40px
multidrug resistance protein 1 ABC transporter B family member 1 DV membrane Transporter of the Dv membrane PfMDR1* ATC451840 Dd2, 7G8, NF54 12- to 56-fold G316R, M841I, M841I and M924I, A807V/T, Y1076F
PFC10_API0055 apicoplast ribosomal protein S4 Apicoplast Protein synthesis Apicoplast LSU rRNA Azithromycin 7G8, Dd2, D10 16- to 17-fold (7G8, Dd2); 57-fold (D10) G76V (7G8 and Dd2), G91D (D10)
PFL1210w
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Image left : 8px, top : 40px
isoleucine--tRNA ligase Apicoplast Protein synthesis Api-IleRS Mupirocin 3D7, HB3 10- to 18-fold P1233S
PF14_0641
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Image left : 8px, top : 40px
1-deoxy-D-xylulose 5-phosphate reductoisomerase Apicoplast Isoprenoid synthesis DXR Fosmidomycin Dd2 8-fold Amplification of pfdxr
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