TABLE 2.
Effect of fluconazole on Sap activity compared with reported mechanisms of resistance for the same isolatesa
| Isolate | MIC (μg/ml) of fluconazoleb | Sap activity with fluconazolec | MDR1 | ERG point mutationd | ERG11e | CDR1e |
|---|---|---|---|---|---|---|
| 1 | 1 | ↓ 3.2 | 0 | 0 | → | → |
| 2 | 2 | ↑ 1.4 | ↑ 12 | 0 | → | → |
| 3 | 8 | ↑ 2.8 | ↑ 25 | 0 | → | → |
| 12 | 8 | ↑ 2.6 | ↑ 25 | 0 | → | → |
| 13 | 16 | ↑ 2.1 | ↑ 25 | + | ↑ 4.5 | → |
| 15 | 32 | ↑ 2.5 | ↑ 25 | + | ↑ 4.5 | → |
| 16 | >64 | ↑ 2.4 | ↑ 25 | + | ↑ 4.5 | ↑ 5 |
| 17 | >64 | ↑ 2.0 | ↑ 25 | + | ↑ 4.5 | ↑ 5 |
As reported by White (38), progressively enhanced expression of MDR1, ERG11, and CDR1 was observed over time for isolates 1 to 17; 0, no gene expression or no point mutation was observed. ↑ and ↓, fold increase or decrease.
Determined by modified NCCLS method M27-A with YCB-BSA medium.
Fold increase (↑) or decrease (↓) of absolute Sap activity for isolates grown in the presence of 1/2 MIC of fluconazole relative to that for the same isolates grown in the absence of fluconazole on the day of peak Sap activity (day 9). Definition of 1/2 MIC for each isolate: 1, 0.5 μg/ml; 2, 1.0 μg/ml; 3 and 12, 4.0 μg/ml; 13, 8.0 μg/ml; 15, 16.0 μg/ml; and 16 and 17, 32.0 μg/ml.
+, point mutation in the ERG11 gene associated with increased azole resistance between isolates 12 and 13 (38).
→, Constitutive expression (38).