TABLE 4.
Correlation between site of mutation, degree of resistance, and fitness cost of various atovaquone resistance mutations
| Isolate | Mutation | Mean IC50 (nM) ± SDa | Mean growth rate (μg mtDNA/ml blood/24 h) ± SD | Fitness cost of resistance (%)b |
|---|---|---|---|---|
| PbL | Wild type | 0.327 ± 0.141 | 9.46 ± 1.10 | Control |
| PbLSJ2.1 | Y268C | 42.5 ± 5.9 | 2.92 ± 0.61 | 69.13 |
| PbLSJ6 | Y268N | 43.5 ± 3.9 | 2.05 ± 0.54 | 78.33 |
| PbLACSN4 | Y268S | ND | 5.26 ± 0.42 | 44.40 |
| PbLASNL1 | M133I | ND | 3.21 ± 0.30 | 66.07 |
| PbSK2A1Tb | M133I/L271V | 20.0 | 5.77 ± 1.45 | 39.01 |
a
IC50s (50% inhibitory concentrations) reported previously (8). ND, not determined.
b
Percent loss of fitness of the mutant strains relative to the wild type calculated from the growth rates; in vivo growth rates were determined by measuring the increase in the level of parasite mtDNA per milliliter of blood over a period of 24 h, as described in Materials and Methods.