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Resistance to experimental antimalarials generated in vitro |
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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 |
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Resistance gene(s) |
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Annotation |
Target location |
Pathway/mechanism |
Target molecule |
Selection compound |
Parent strain |
IC50 increase |
Genetic changes |
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| 29649 |
PF3D7_1211900 |
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non-SERCA-type Ca2+ -transporting P-ATPase, ATP4 |
Plasma membrane |
Ion homeostasis |
PfATP4 |
KAE609 |
Dd2 |
2 to 33–fold |
>36 SNPs identified |
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SJ557733 |
3D7, Dd2 |
3 to 480–fold |
L350H, P412T, V415D |
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21A092 |
Dd2 |
20–fold |
V178I |
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| 29653 |
PF3D7_1341900 |
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V-type proton ATPase subunit D, putative |
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pH regulation |
V-type H+-ATPase |
AZ412 |
Dd2 |
3 to 6-fold |
G29V |
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| 29656 |
PF3D7_1451100 |
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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 |
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| 29646 |
PF3D7_0622800 |
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leucine--tRNA ligase, putative |
Cytoplasm |
Protein synthesis |
LeuRS |
AN6426 |
Dd2 |
1.5- to 60-fold |
T400I, V568L, E628G, V630L |
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| 29652 |
PF3D7_1332900 |
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isoleucine--tRNA ligase, putative |
Cytoplasm |
Protein synthesis |
Cyto-IleRS |
Thiaisoleucine |
3D7 |
2-fold |
L810F |
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| 29650 |
PF3D7_1213800 |
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prolyl-tRNA synthetase proline--tRNA ligase |
Cytoplasm |
Protein synthesis |
ProRS |
Halofuginone |
Dd2 |
60- to 360-fold |
L482H/F |
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| 29654 |
PF3D7_1350100 |
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lysine--tRNA ligase |
Cytoplasm |
Protein synthesis |
LysRS |
Cladosporin |
Dd2 |
6-fold |
Amplification of pfKrs1 |
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| 29641 |
PF3D7_0109800 |
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phenylalanyl-tRNA synthetase alpha subunit |
Cytoplasm |
Protein synthesis |
PheRS |
BRD1095 and BRD7929 |
Dd2 |
4- to 84-fold |
M316I, L550V, G512E and V545I |
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| 29655 |
PF3D7_1438500 |
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cleavage and polyadenylation specificity factor subunit 3, putative |
Nucleus |
mRNA processing |
CPSF3 |
AN3661 |
Dd2, W2 |
11–to 200–fold |
H36Y, T406I, Y408S, T409A, D470N, amplification pfcpsf3 |
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| 29642 |
PF3D7_0321900 |
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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 |
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| 29648 |
PF3D7_1113300 |
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UDP-galactose transporter, putative, UGT |
Endoplasmic reticulum and Golgi apparatus |
transporter of ER membrane |
Unknown |
KAF156 and analogues |
3D7, Dd2 |
6- to 890-fold |
F37V |
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| 29647 |
PF3D7_1036800 |
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acetyl-CoA transporter, putative, ACT |
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 |
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| 29643 |
PF3D7_0509800 |
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phosphatidylinositol 4-kinase beta |
Endomembrane system |
Membrane trafficking |
PI4K |
KAI407 |
Dd2 |
2- to 10-fold |
H1484Y, amplification of pfpi4k |
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| 29643 |
PF3D7_0509800 |
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phosphatidylinositol 4-kinase beta |
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MMV390048 |
Dd2 |
4- to 5–fold |
S743T, A1319V |
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| 29658 |
mal_mito_3 |
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apocytochrome b (cyb) |
Mitochondrion |
Electron transport |
CYTb |
ELQ-300 |
Dd2 |
24-fold |
I22L |
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| 29658 |
mal_mito_3 |
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apocytochrome b (cyb) |
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Decoquinate |
3D7 |
90-fold |
A122T and Y126C |
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| 29645 |
PF3D7_0603300 |
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dihydroorotate dehydrogenase |
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Pyrimidine biosynthesis |
DHODH |
DSM265 |
Dd2, K1 |
3- to 32-fold |
G181C, amplification of pfdhodh |
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| 29644 |
PF3D7_0523000 |
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multidrug resistance protein 1. MDR1, IP3 receptor |
DV membrane |
Transporter of the Dv membrane |
PfMDR1* |
ATC451840 |
Dd2, 7G8, NF54 |
12- to 56-fold |
G316R, M841I, M841I and M924I, A807V/T, Y1076F |
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| 29659 |
PFC10_API0055 |
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apicoplast ribosomal protein S4 (rps4) |
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) |
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| 29651 |
PF3D7_1225100 |
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isoleucine--tRNA ligase, putative |
Apicoplast |
Protein synthesis |
Api-IleRS |
Mupirocin |
3D7, HB3 |
10- to 18-fold |
P1233S |
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| 29657 |
PF3D7_1467300 |
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1-deoxy-D-xylulose 5-phosphate reductoisomerase |
Apicoplast |
Isoprenoid synthesis |
DXR |
Fosmidomycin |
Dd2 |
8-fold |
Amplification of pfdxr |
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