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
27432 PF3D7_1211900
non-SERCA-type Ca2+ -transporting P-ATPase, ATP4 Plasma membrane Ion homeostasis KAE609 Dd2 <8 (multiple strains) 2 to 33–fold >36 SNPs identified
27432 PF3D7_1211900
non-SERCA-type Ca2+ -transporting P-ATPase, ATP4 Plasma membrane SJ557733 3D7, Dd2 7 (3D7) 3 to 480–fold L350H, P412T, V415D
27432 PF3D7_1211900
non-SERCA-type Ca2+ -transporting P-ATPase, ATP4 Plasma membrane 21A092 Dd2 <9.5 (Dd2) 20–fold V178I
27436 PF3D7_1341900
V-type proton ATPase subunit D, putative pH regulation pH regulation AZ412 Dd2 <10 (Dd2) 3 to 6-fold G29V
27439 PF3D7_1451100
elongation factor 2 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
27431 PF3D7_0622800
leucine--tRNA ligase, putative Protein synthesis Protein synthesis AN6426 Dd2 8 (Dd2) 1.5- to 60-fold T400I, V568L, E628G, V630L
27435 PF3D7_1332900
isoleucine--tRNA ligase, putative Protein synthesis Protein synthesis Thiaisoleucine 3D7 nd 2-fold L810F
27433 PF3D7_1213800
prolyl-tRNA synthetase proline--tRNA ligase Protein synthesis Protein synthesis Halofuginone Dd2 nd 60- to 360-fold L482H/F
27437 PF3D7_1350100
lysine--tRNA ligase Protein synthesis Protein synthesis Cladosporin Dd2 nd 6-fold Amplification of pfKrs1
27427 PF3D7_0109800
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
27438 PF3D7_1438500
cleavage and polyadenylation specificity factor subunit 3, putative mRNA processing mRNA processing AN3661 Dd2, W2 6 (Dd2) 11–to 200–fold H36Y, T406I, Y408S, T409A, D470N, amplification pfcpsf3
27443 PF3D7_0321900
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
27444 PF3D7_1113300 UDP-galactose transporter, putative, UGT 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
27445 PF3D7_1036800 acetyl-CoA transporter, putative, ACT 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
27428 PF3D7_0509800
phosphatidylinositol 4-kinase beta Membrane trafficking Membrane trafficking KAI407 Dd2 nd 2- to 10-fold H1484Y, amplification of pfpi4k
MMV390048 Dd2 6 (Dd2) 4- to 5–fold S743T, A1319V
27441 mal_mito_3
apocytochrome b (cyb) Electron transport Electron transport ELQ-300 Dd2 <8 (Dd2) 24-fold I22L
Decoquinate 3D7 nd 90-fold A122T and Y126C
27430 PF3D7_0603300
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
27429 PF3D7_0523000
multidrug resistance protein 1. MDR1 Unknown Unknown ATC451840 Dd2, 7G8, NF54 6 (Dd2), 7 (7G8 and NF54) 12- to 56-fold G316R, M841I, M841I and M924I, A807V/T, Y1076F
27442 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)
27434 PF3D7_1225100
isoleucine--tRNA ligase, putative Protein synthesis Protein synthesis Mupirocin 3D7, HB3 nd 10- to 18-fold P1233S
27440 PF3D7_1467300
1-deoxy-D-xylulose 5-phosphate reductoisomerase Isoprenoid synthesis Isoprenoid synthesis Fosmidomycin Dd2 nd 8-fold Amplification of pfdxr
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