Table 3.
Kinetic constants for M. tuberculosis l,d-transpeptidase inactivation by carbapenems
| l,d-Transpeptidase and kinetic constant | Value (mean ±SD) for: |
|||
|---|---|---|---|---|
| Imipenem | Meropenem | Ertapenem | Doripenem | |
| Mt1 | ||||
| k1 × 103 (μM−1 min−1) | 460 ± 20 | 64 ± 2 | 930 ± 60 | 130 ± 10 |
| k2 × 103 (min−1) | 1,810 ± 20 | 3,600 ± 80 | 2,660 ± 50 | 470 ± 20 |
| k2/Kapp × 103 (μM−1 min−1) | 610 ± 20 | 75 ± 2 | 1,350 ± 50 | 89 ± 4 |
| k3 × 103 (min−1) | ≤0.12 | 1.04 ± 0.09 | 1.01 ± 0.12 | 0.58 ± 0.09 |
| Mt2 | ||||
| k1 × 103 (μM−1 min−1) | 67 ± 5 | 0.67 ± 0.02 | 4.0 ± 0.1 | 0.85 ± 0.04 |
| k2 × 103 (min−1) | 11,200 ± 700 | 660 ± 40 | 1,010 ± 30 | 580 ± 30 |
| k2/Kapp × 103 (μM−1 min−1) | 81 ± 2 | 0.48 ± 0.01 | 3.6 ± 0.1 | 0.56 ± 0.02 |
| k3 × 103 (min−1) | ≤0.06 | 0.72 ± 0.03 | 0.48 ± 0.08 | 0.34 ± 0.05 |
| Mt3 | ||||
| k1 × 103 (μM−1 min−1) | 920 ± 30 | 17 ± 1 | 87 ± 3 | 10.2 ± 0.5 |
| k2 × 103 (min−1) | 10,100 ± 200 | 6,800 ± 700 | 6,500 ± 600 | 4,500 ± 300 |
| k2/Kapp × 103 (μM−1 min−1) | 1,160 ± 30 | 21 ± 1 | 80 ± 2 | 12 ± 1 |
| k3 × 103 (min−1) | ≤0.12 | 1.42 ± 0.26 | 1.02 ± 0.06 | 0.38 ± 0.01 |
| Mt4 | ||||
| k1 × 103 (μM−1 min−1) | 250 ± 10 | 5.0 ± 0.3 | 31 ± 3 | NAa |
| k2 × 103 (min−1) | 9,900 ± 300 | 80 ± 20 | 18,000 ± 1,000 | NA |
| k2/Kapp × 103 (μM−1 min−1) | 310 ± 10 | 0.67 ± 0.024 | 37 ± 1 | 9.7 ± 1.7 |
| k3 × 103 (min−1) | ≤0.06 | 5.6 ± 0.6 | 3.9 ± 0.7 | 0.61 ± 0.27 |
a
NA, not applicable (constants k1 and k2 could not be determined since fluorescence kinetics were monophasic).