Table 1.
Resistance profiles for strains with DHFR mutations
| Inhibitor | DHFR mutation [no. of colonies containing mutations/total no. of colonies recovered] | Single nucleotide polymorphisma | Mutation frequency (± SD) | Wild-type MIC (μg/ml) | Mutant MIC (μg/ml) | Fold potency lossb | Fitness ratio (± SD)c |
|---|---|---|---|---|---|---|---|
| TMP | F98Y [5/7] | TTT to TAT | 1.65 × 10−9 (± 0.39) | 0.625 | 10 | 16 | 0.982 (± 0.097) |
| 1 | F98I [4/14] | TTT to ATT | 6.87 × 10−10 (± 2.3) | 0.078 | 2.5 | 32 | 1.04 (± 0.23) |
| F98Y [7/14] | TTT to TAT | 1.20 × 10−9 (± 0.19) | 0.078 | 2.5 | 32 | 0.993 (± 0.21) | |
| 2 | H30N [5/11] | CAT to AAT | 8.88 × 10−10 (± 0.50) | 1.25 | 20 | 16 | 0.974 (± 0.26) |
| F98Y [4/11] | TTT to TAT | 7.10 × 10−10 (± 0.53) | 1.25 | 20 | 16 | 0.993 (± 0.21) |
a
The single nucleotide polymorphisms are indicated in bold.
b
Fold potency loss = (MICMutant/MICParent).
c
Fitness ratios represent the relative fitness of mutants compared to the wild type determined using pair-wise competition assays as described by Lenski et al. (18).