Table 3.
Characteristics of spontaneous PIPD1-resistant mutants of M. tuberculosis
The MICs against M. tuberculosis mc26230 and the resistant mutants derived from mc26230 were obtained in several independent experiments and selected after 3 weeks of incubation at 37 °C on Middlebrook 7H10 containing OADC enrichment and 24 μg/ml pantothenate. Selection was done in the presence of 0.25, 0.5, or 1 μg/ml PIPD1 or 2 μg/ml FMD88. SNP in mmpL3 as well as the corresponding amino acid changes are also indicated. The number of mutants as well as the frequency for each mutation are indicated. AA, amino acid.
| Strain | MIC | MIC | Fold change | Number of mutants | Frequency | Mutation in mmpL3 |
|
|---|---|---|---|---|---|---|---|
| SNP description | AA change | ||||||
| μg/ml | μm | ||||||
| mc26230 | 0.125 | 0.32 | |||||
| mc26230_R1 | 0.5 | 1.28 | 4 | 29 | 2.7E-06 | A1945C | M649L |
| mc26230_R2 | 0.5 | 1.28 | 4 | 2 | 1.8E-07 | C2111T | M704T |
| mc26230_R3 | 0.25 | 0.64 | 2 | 1 | 9.2E-08 | G769T | V257L |
| mc26230_R4 | 2 | 5.12 | 16 | 1 | 9.2E-08 | T875C | I292T |
| mc26230_R5 | 1 | 2.56 | 8 | 1 | 9.2E-08 | T1700C | L567P |
| mc26230_R6 | 0.5 | 1.28 | 4 | 3 | 2.8E-07 | T854C | V285A |
| mc26230_R7 | 4 | 10.24 | 32 | 9 | 8.3E-07 | T754G | Y252D |
| mc26230_R8 | 0.5 | 1.28 | 4 | 1 | 9.2E-08 | C625G | P209A |
| mc26230_R9 | 1 | 2.56 | 8 | 1 | 9.2E-08 | G2041A | V681I |
| mc26230_R10 | 0.5 | 1.28 | 4 | 1 | 9.2E-08 | T854G | V285G |