TABLE 2.
In vitro selection of MexXY-OprM-overexpressing mutants from susceptible P. aeruginosa isolates
| Strain(s) and selecting antibiotic (concn [μg/ml])a | Frequency of MexXY-OprM-overexpressing mutants | Mutant characteristicsb
|
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|---|---|---|---|---|---|---|---|
| mexY expression (type of mutant)c | MIC (μg/ml) of:
|
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| GEN | TOB | AMK | CIP | FEP | |||
| PAO1 | 1.0 | 4 | 1 | 4 | 0.12 | 2 | |
| AMK (8) | 8 × 10−7 | 70.7 (agrW) | 8-16 | 2-4 | 8-32 | 0.5 | 4-8 |
| TOB (1) | 2 × 10−7 | 47.6 (agrZ) | 8-16 | 2-4 | 8-32 | 0.5 | 4-8 |
| GEN (4) | 8 × 10−7 | 51.6 (agrZ) | 8-16 | 2-4 | 8-32 | 0.5 | 4-8 |
| OFX (1) | 7 × 10−7 | 38.9 (agrW) | 8-16 | 2-4 | 8-32 | 0.5 | 4-8 |
| NOR (1) | 1 × 10−6 | 63.1 (agrZ) | 8-16 | 2-4 | 8-32 | 0.5 | 4-8 |
| CIP (0.25) | 5 × 10−8 | 18.3 (agrW) | 8-16 | 2-4 | 8-32 | 0.5 | 4-8 |
| FEP (4) | 2 × 10−7 | 36.4 (agrW) | 8-16 | 2-4 | 8-32 | 0.5 | 4-8 |
| Clinical isolates (n = 7) | 0.5-3.1 | 2-4 | 1 | 4 | 0.06-0.25 | 1-2 | |
| AMK (8) | 6 × 10−7-1 × 10−7 | 7.2-93.2 | 8-16 | 2-4 | 8-32 | 0.5 | 4-8 |
| CIP (0.25) | 9 × 10−7-4 × 10−7 | 13.8-343.3 | 8-16 | 2-4 | 8-32 | 0.5 | 4-8 |
| FEP (4) | 3 × 10−8-8 × 10−7 | 21.1-26.6 | 8-16 | 2-4 | 8-32 | 0.5 | 4-8 |
The antibiotics that do not appear here do not select for PA/XY mutants (selection rates < 10−11) (MICs are in parentheses): amoxicillin with or without clavulanic acid (32/4 μg/ml), aztreonam (4 μg/ml), azithromycin (4 μg/ml), cefotaxime (32 μg/ml), cefoxitin (4,096 μg/ml), ceftazidime (2 μg/ml), ceftriaxone (32 μg/ml), cefuroxime (256 μg/ml), chloramphenicol (64 μg/ml), cloxacillin (4,096 μg/ml), colistin (2 μg/ml), ertapenem (4 μg/ml), erythromycin (256 μg/ml), fosfomycin (256 μg/ml), imipenem (1 μg/ml), linezolid (2,048 μg/ml), meropenem (0,5 μg/ml), piperacillin (16 μg/ml), piperacillin plus tazobactam (4/0,5 μg/ml), rifampin (32 μg/ml), teicoplanin (1,024 μg/ml), ticarcillin with or without clavulanic acid (16/1,07 μg/ml), trimethoprim plus sulfamethoxazole (128 μg/ml), vancomycin (1,024 μg/ml). AMK, amikacin; TOB, tobramycin; GEN, gentamicin; CIP, ciprofloxacin; NOR, norfloxacin; OFX, ofloxacin; FEP, cefepime.
One mutant per strain and per antibiotic was characterized. Substitutions (GCC→ACC, A20T; TAC→TAA, Y204stop; AAC→AGC, N186S) or 1-bp deletions (A80 and C605 for two mutants) were observed in the mexZ gene.
Expression relative to PAO1; mean values from two independent experiments.