TABLE 2.
First- and second-step and compensatory mutations associated with mupirocin resistance and their associated effects on resistance and competitive fitness in S. aureusa
| Mutant and amino acid substitution in IleRSb | Mupirocin MIC (μg/ml) | Competitive fitness |
|---|---|---|
| Wild type | 0.016 | 1.00 |
| First-step mupirocin-resistant mutants | ||
| G593V | 1 | 0.92 ± 0.02 |
| G593V | 2 | 0.94 ± 0.05 |
| V631F | 2 | 0.99 ± 0.08 |
| V631F | 2 | 1.00 ± 0.03 |
| V588F | 8 | 0.94 ± 0.04 |
| V588F | 8 | 0.95 ± 0.01 |
| V588F | 8 | 0.93 ± 0.01 |
| V588F | 8 | 0.96 ± 0.05 |
| V588F | 16 | 0.99 ± 0.03 |
| V588F | 16 | 0.94 ± 0.04 |
| Second-step mupirocin-resistant mutants | ||
| G593V, V631F | 16 | 0.63 ± 0.03 |
| V631F, V588F | 32 | 0.57 ± 0.03 |
| V588F, R816C | 64 | 0.32 ± 0.06 |
| V588F, F563L | 128 | 0.24 ± 0.08 |
| V588F, H67Q | 128 | 0.33 ± 0.01 |
| Fitness-restored mutants | ||
| G593V, V631F, A196V | 2 | 0.99 ± 0.02 |
| G593V, V631F, A196V | 2 | 0.94 ± 0.07 |
| G593V, V631F, E190K | 2 | 1.00 ± 0.00 |
| G593V, V631F, E190K | 2 | 1.00 ± 0.01 |
| V631F, V588F, none | 32 | 1.01 ± 0.05 |
| V588F, R816C, E195K | 4 | 0.95 ± 0.01 |
| V588F, R816C, A196V | 8 | 0.93 ± 0.08 |
| V588F, F563L, none | 8 | 0.98 ± 0.01 |
| V588F, H67Q, Q67H | 8 | 0.96 ± 0.05 |
| V588F, H67Q, H396Q | 8 | 0.79 ± 0.07 |
| V588F, H67Q, H396Q | 16 | 0.79 ± 0.07 |
a
The table is based on data presented elsewhere (48).
b
The mutations in IleRS occurring at each stepwise selection are shown in boldface.