Table 2. Drug sensitivity profile of Tb427WT cells expressing either the wild-type F1 subunit γ gene, or the same gene with mutation S284*, either exposed to ethidium bromide or ISM, or not exposed to any trypanocide.
WT ATPase γ | S284* ATPase γ Unexposed | S284* ATPase γ Isometamidium Exposed | S284* ATPase γ Ethidium Bromide Exposed | ||||||
---|---|---|---|---|---|---|---|---|---|
Compound | Mean EC50 (nM) | Mean EC50 (nM) | Resistance Factor vs. WT ATPase γ | Mean EC50 (nM) | Resistance Factor vs. WT ATPase γ | Resistance Factor vs. Unexposed | Mean EC50 (nM) | Resistance Factor vs. WT ATPase γ | Resistance Factor vs. Unexposed |
Isometamidium | 0.31 ± 0.06 | 31.9 ± 6.1 | 104* | 172 ± 59 | 560*** | 5.4*** | 162 ± 46 | 529*** | 5.1*** |
Ethidium Bromide | 1.49 ± 0.21 | 554 ± 50 | 372*** | 361 ± 16 | 242*** | 0.65 | 322 ± 36 | 216*** | 0.58 |
Diminazene | 20.3 ± 0.8 | 108 ± 6.4 | 5.3** | 132 ± 24 | 6.5*** | 1.2 | 136 ± 26 | 6.7*** | 1.3 |
Pentamidine | 2.8 ± 0.3 | 7.22 ± 0.66 | 2.6** | 2.3 ± 0.3 | 0.82 | 0.32 | 2.38 ± 0.73 | 0.84 | 0.33 |
Oligomycin | 270 ± 33 | 1410 ± 90 | 5.2*** | 872 ± 282 | 3.2** | 0.62 | 1180 ± 170 | 4.4*** | 0.83 |
Asterisks represent P-values for statistically significant resistance, as calculated using a one-tailed Student’s t-test:
*, P-value <0.05;
**, P-value <0.01;
***, P-value <0.001.