TABLE 2.
Susceptibility of mmpL5 loss-of-function and gain-of-function strains to 16 antibioticsa
| Antibiotic | Target process | mmpL5 Tyr300Stop |
mmpL5 Tyr300Stop + pNative:mmpS5/L5 |
mmpL5 Tyr300Stop + pHsp60:mmpS5/L5 | IC50 ratiob |
|---|---|---|---|---|---|
| PBTZ169 | Arabinogalactan | 1.0 | 1.2 | 4.7 | 3.9 |
| BTZ043 | Arabinogalactan | 3.1 | 3.5 | 7 | 2 |
| Bedaquiline | ATP synthase | 33 | 160 | 1400 | 8.8 |
| Clofazimine | Respiration | 100 | 170 | 1030 | 6.1 |
| Rifampicin | Transcription | 7.2 | 7.8 | 7.3 | 0.9 |
| Isoniazid | Mycolic acid | 9.3 | 9.7 | 9.7 | 1.0 |
| TCA-1 | Arabinogalactan | 3800 | 3800 | 3500 | 0.9 |
| IN-2 | Arabinogalactan | 2700 | 2700 | 3100 | 1.1 |
| Ethambutol | Arabinogalactan | 1900 | 1900 | 2300 | 1.2 |
| Levofloxacin | DNA replication | 900 | 960 | 970 | 1.0 |
| Pretomanid | Mycolic acid | 750 | 810 | 830 | 1.0 |
| Linezolid | Translation | 1100 | 1100 | 1200 | 1.1 |
| Fusidic Acid | Translation | 1800 | 3400 | 15000 | 4.4 |
a
IC50 values reflect drug concentrations in nanomolar (nM).
b
The IC50 ratio was calculated by dividing the IC50 for the pHsp60-driven mmpS5/L5 strain by the IC50 for the pNative-driven mmpS5/L5 strain.