TABLE 1.
Susceptibility profiles of the PAΔA strain complemented with the different PDC variants
| Straina | MIC (μg/mL)b |
||||||||
|---|---|---|---|---|---|---|---|---|---|
| CAZ (R at ≥32 μg/mL) | CTZ (R at ≥16 μg/mL) | CTZ/TZ (R at ≥16/4 μg/mL) | AZT (R at ≥32 μg/mL) | PIP (R at ≥128 μg/mL) | PIP/TZ (R at ≥128/4 μg/mL) | FEP (R at ≥32 μg/mL) | IMP (R at ≥8 μg/mL) | MEM (R at ≥8 μg/mL) | |
| PAO1 | 2 | 1 | 1 | 8 | 16 | 8 | 4 | 2 | 1 |
| PAΔA | 2 | 1 | 1 | 8 | 16 | 8 | 4 | 1 | 1 |
| PAΔA-EV | 1 | 1 | 1 | 4 | 4 | 4 | 2 | 0.5 | 0.5 |
| PAΔA-1 | 4 | 1 | 1 | 8 | 64 | 16 | 4 | 1 | 1 |
| PAΔA-3(T79A) | 4 | 1 | 1 | 4 | 64 | 16 | 4 | 1 | 1 |
| PAΔA-458(G214S, V329I) | 4 | 2 | 1 | 16 | 16 | 8 | 2 | 1 | 1 |
| PAΔA-459(Q120K, P153L, V211A) | 128 | 32 | 8 | 128 | 32 | 16 | 4 | 1 | 1 |
| PAΔA-460(A89V, V211A, N320S) | 32 | 2 | 1 | 16 | 64 | 16 | 4 | 1 | 1 |
| PAΔA-461(A89V, Q120K, V211A) | 128 | 16 | 16 | 32 | 8 | 2 | 8 | 1 | 1 |
| PAΔA-462(A89V, Q120K, V211A, N320S) | 128 | 8 | 8 | 64 | 64 | 16 | 4 | 1 | 1 |
| PAΔA-463(A89V, H188Y, Q120K, V211A) | 64 | 8 | 4 | 128 | 32 | 16 | 4 | 2 | 1 |
| PAΔA-464(A89V, H188Y, Q120K, V211A, N320S) | 64 | 8 | 4 | 16 | 64 | 16 | 4 | 1 | 1 |
blaPDC allelic variants (PDC-3 and PDC-458 to PDC-464) were cloned into the pMBLe vector and transformed into the PAΔA strain. The PAΔA strain expressing the PDC variant from PAO1 (i.e., PAΔA-1) or the empty vector (i.e., PAΔA-EV) was used as a control.
CAZ, ceftazidime; CTZ, ceftolozane; CTZ/TZ, ceftolozane-tazobactam at 2:1; AZT, aztreonam; PIP, piperacillin; PIP/TAZ, piperacillin-tazobactam at a fixed concentration of 4 μg/mL; FEP, cefepime; IMP, imipenem; MEM, meropenem. The resistance (R) thresholds are shown in parentheses for each drug or combination. Shown are values from at least two independent experiments. Values of MICs of PAΔA-3 and PAΔA-461 to -463 are highlighted in bold for comparisons with the kinetic parameters obtained for the CAZ, CTZ, PIP, and IMP antibiotics.