TABLE 6.
Impact of different LpxC target mutations on susceptibility to LpxC inhibitor scaffolds
| Strain | LpxC variant | MIC (μg/ml)a
|
||||
|---|---|---|---|---|---|---|
| CHIR-090 | Compound 3 | Compound 2 | MER | TOB | ||
| K767 | LpxCWT | 1 | 0.50 | 0.25 | 1 | 0.125 |
| K767-CDR0026 | LpxCWT upregulated | 16 | 16 | 8 | 1 | 0.25 |
| K767-CDJ0011 | LpxCL18V | 8 | 0.5 | 1 | 1 | 0.25 |
| K767-LpxCG208S | LpxCG208S | 4 | 0.125 | 0.125 | 0.5 | 0.125 |
| K767-CDJ0037 | LpxCA214V | 0.5 | >16 | 4 | 0.5 | 0.125 |
| PAO1V | LpxCWT | 1 | 0.25 | 0.25 | 1 | 0.125 |
| PAO1V-CDJ0042 | LpxCA214V | 0.5 | 16 | 2 | 1 | 0.125 |
a
Susceptibility shifts ≥ 4-fold are indicated in boldface. MER, meropenem; TOB, tobramycin.