Table 1.
Mutations in ERG11 and ERG3 genes, corresponding amino acid substitutions, and MICs of antifungal drugs for Candida tropicalis isolates
| Isolate | Previous treatmenta | Gene sequence analysisb |
MIC (μg/ml)c |
||||||
|---|---|---|---|---|---|---|---|---|---|
| 14α-Sterol demethylase |
Sterol Δ5,6-desaturase |
||||||||
| ERG11 (bp) | Erg11p (aa) | ERG3 (bp) | Erg3p (aa) | AMB | FLC | VRC | ANF | ||
| ATCC 750 | Unknown | G366A | R122R | 0.25 | 0.5 | 0.03 | 0.03 | ||
| ATCC 200956 | Unknown | Δ132 bp | Δ44 aa | C773T | S258F | 2 | >64 | >8 | 0.03 |
| —d | D275V | ||||||||
| G1362A | K454K | ||||||||
| C1534G | P511A | ||||||||
| T1554C | I517I | ||||||||
| CL-6835 (clinical) | FLC, AMB, and CAS | T906C | I302I | A334G | S113G | 2 | >64 | >8 | 0.03 |
| G1391A | G464D | G366A | R122R | ||||||
| T637C | L212L | ||||||||
| TP-13650 (clinical) | FLC, VRC, and TRB | T225C | C75C | 0.25 | >64 | >8 | 0.03 | ||
| G264A | L88L | ||||||||
| A395T | Y132F | ||||||||
| T783C | I261I | ||||||||
| G1362A | K454K | ||||||||
| T1554C | I517I | ||||||||
CAS, caspofungin; TRB, terbinafine.
Substitutions in amino acid sequences are shown in boldface.
Determined by broth microdilution according to the established method of AFST-EUCAST. AMB, amphotericin B; FLC, fluconazole; VRC, voriconazole; ANF, anidulafungin. EUCAST antifungal clinical breakpoints for C. tropicalis are as follows: for AmB, ≤1 μg/ml for susceptibility and >1 μg/ml for resistance; for FLC, ≤2 μg/ml for susceptibility and >4 μg/ml for resistance; for VRC, ≤0.12 μg/ml for susceptibility and >0.12 μg/ml for resistance; and for ANF, ≤0.06 μg/ml for susceptibility and >0.06 μg/ml for resistance.
—, 132-bp deletion, between nucleotides 824 and 945, results in a 44-amino-acid deletion, between aa 276 and 319. The change in the open reading frame is the cause of the D275V amino acid substitution.