Table 3.
Susceptibilities of M. tuberculosis WT and Rv1258c, Rv1218c, Rv0849, and Rv3065 KO mutants to compounds in the presence and absence of efflux inhibitors
| Compound | MIC (μg/ml) for M. tuberculosis strain: |
||||
|---|---|---|---|---|---|
| WT | KO1 | KO5 | KO6 | KO7 | |
| Pyrroles | |||||
| AZI-533 | 0.03 | 0.016 | 0.004–0.008 | 0.008–0.016 | 0.008 |
| AZI-533 + verapamil | 0.008 | 0.008 | 0.004 | 0.004 | 0.004 |
| AZI-533 + PAβN | 0.016 | 0.004 | 0.004 | 0.004 | 0.002 |
| AZI-530 | 0.25 | 0.125 | 0.03 | 0.06 | 0.03 |
| AZI-530 + verapamil | 0.06 | 0.06 | 0.03 | 0.03 | 0.016 |
| AZI-530 + PAβN | 0.125 | 0.03 | 0.03 | 0.06 | 0.016 |
| Pyrazolones | |||||
| AZI-219 | 256 | 128–256 | 64–128 | 128–256 | 128–256 |
| AZI-219 + verapamil | 16–32 | 16–32 | 8–16 | 8–16 | 16–32 |
| AZI-219 + PAβN | 32 | 32 | 32 | 128 | 16-32 |
| AZI-335 | 1 | 1 | 0.5 | 0.5 | 0.5–1 |
| AZI-335 + verapamil | 0.5 | 0.5 | 0.25 | 0.25 | 0.25 |
| AZI-335 + PAβN | 0.5 | 0.5 | 0.125 | 0.25-0.5 | 0.5 |
| Other drugs | |||||
| Clofazimine | 0.125–0.25 | 0.06–0.125 | 0.06–0.125 | 0.06–0.125 | 0.03–0.06 |
| Clofazimine + verapamil | 0.03 | 0.03 | 0.016 | 0.016–0.03 | 0.008–0.016 |
| Clofazimine + PAβN | 0.016 | 0.03 | 0.016 | 0.06 | 0.016 |
| Efflux inhibitors | |||||
| Verapamil | >200 | >200 | >200 | >200 | >200 |
| PAβN | 32 | 16 | 16 | 16 | 16 |
MICs were determined by the resazurin-based microplate assay. Each reported value is the average of at least 2 independent assays. The efflux inhibitors verapamil and PAβN were added at 50 μg/ml and 4–8 μg/ml (subinhibitory) concentrations where required.