Table 2.
Point mutations in drug-resistant parasite lines arising from in vivo selection experiments with resulting EC50 values (nM). Point mutation and dose-response phenotype listed for each in vitro–selected clone. EC50 values (nM) represent an average of two to five biological replicates ± SD. Where two biological replicates were performed, only mean is reported (table S2 and data file S1). CNVs were determined by whole-genome sequencing and confirmed by qPCR (fig. S6).
| In vivo selection of 3D70087/N9 treated with DSM265 | ||||
|---|---|---|---|---|
| Clone ID | DHODH mutations |
Copy no. | DSM265 EC50 |
|
| 3D70087/N9 | N/A | 1 | 25.0 ± 4.73 | |
| Group A | RPA-C1 | C276F | 1 | 655 ± 317 |
| RPA-C2 | C276F | 1 | 684 ± 169 | |
| RPA-C3 | R265G | 1 | 966 ± 314 | |
| RPA-C4 | R265G | 1 | 669 ± 238 | |
| Group B | RPB-C1 | G181D | 1 | 3419 |
| RPB-C2 | G181D | 1 | 3173 | |
| RPB-C3 | G181D | 1 | 3346 | |
| RPB-C4 | G181D | 1 | 3098 | |
| Group D | RPD-C1 | G181D | 1 | 3060 |
| RPD-C2 | G181D | 1 | 3360 | |
| RPD-C3 | G181D | 1 | 3240 | |
| RPD-C4 | G181D | 1 | 1800 | |