Table 2.
Cross-resistance and whole genome sequencing analysis of 4-hydroxy-2-pyridone resistance mutants of Mtb.
| Strains | inhA genotype | Catalase phenotype* | Compound MIC50 (μM) | |||||
|---|---|---|---|---|---|---|---|---|
|
|
||||||||
| NITD-529 | NITD-564 | NITD-916 | I | E | S | |||
| Mutation frequency | - | - | 1.2×10-8 | - | 1.0×10-8 | ∼ 1× 10-6 | - | - |
|
| ||||||||
| H37Rv WT | WT | + | 1.54 | 0.16 | 0.05 | 0.25 | 1.66 | 0.08 |
| 529-B2 | tcg to gcg S94A | + | > 40 | 4.04 | 0.78 | 0.86 | 9.74 | 0.06 |
| 529-S3 | gac to ggc D148G | + | > 40 | 1.73 | 0.38 | 0.15 | - | 0.08 |
| 529-B4 | ggg to gtg G96V | + | > 40 | 14.60 | > 5.0 | 0.09 | 1.32 | 0.1 |
| 529-B6 | - | + | > 40 | > 40 | > 5.0 | 0.11 | 1.41 | 0.09 |
| 529-B8 | gac to gaa D148E | + | > 40 | > 40 | > 5.0 | 0.31 | 1.91 | 0.08 |
| H37Rv∷pMV262-InhA | inhA∷inhA | nd | 2.59 (1.7×) | - | 0.108 (2.2×) | 0.51 (2.04×) | - | 0.074 |
| H37Rv∷pMV262-InhA∷D148G | inhA∷inhAD148G | nd | > 60 (> 38×) | - | 3.08 (60×) | - | - | 0.084 |
| H37Rv∷pMV262-InhA∷D148E | inhA∷inhAD148E | nd | > 60 (> 38×) | - | > 6.6 (> 100×) | - | - | 0.079 |
| H37Rv∷pMV262-InhA∷S94A | inhA∷inhAS94A | nd | 28.71 (18 ×) | - | 2.40 (48×) | - | - | 0.075 |
In genetically complemented strains, MIC50 fold shift with the Mtb H37Rv strain is given in parentheses,
*
+ ve for catalase activity; nd – not determined. I, Isoniazid, E, Ethionamide, S, Streptomycin.