Table 1.
Consecutive and coexisting isolates from five patients and from laboratory evolution experiments with different macroscopic morphology, azole-resistance mutations and resistance phenotype. —, information is not available.
| strains | isolation date | specimen | treatment/exposurea | spore size (µm) | growth rate on MEA (cm d−1) | azole-resistance mutationsd | MIC (resistance level)b | |||
|---|---|---|---|---|---|---|---|---|---|---|
| ITR | VOR | POS | ||||||||
| P1 | V74-61 | 29 Sep 2008 | sputum | ITC | 2.55 ± 0.02 | 9.375 ± 0.03 | CYP51A(A9T) | 0.5 | 1 | 0.063 |
| V77-41 | 17 Dec 2008 | sputum | POS | 2.65 ± 0.01 | 8.125 ± 0.02 | CYP51A(A9T/F291I) | >16 | 1 | 1 | |
| V80-28 | 9 Mar 2009 | sputum | POS | 2.65 ± 0.01 | 6.875 ± 0.01 | CYP51A(A9T/F291I) | >16 | 8 | >16 | |
| V83-14 | 7 Jun 2009 | BALc | L -AMB + CAS | 2.70 ± 0.01 | 6.625 ± 0.01 | CYP51A(A9T/G54E) | >16 | 0.5 | 1 | |
| P2 | V67-35 | 0 week | respiratory | VOR | 2.50 ± 0.02 | 10.25 ± 0.04 | NC | 0.125 | 0.5 | 0.016 |
| V67-36 | 108 weeks | respiratory | CAS + POS | 2.72 ± 0.01 | 8.875 ± 0.02 | NC | 0.25 | 0.5 | 0.031 | |
| V67-37 | 125 weeks | respiratory | CAS + POS | 2.87 ± 0.02 | 8.375 ± 0.03 | HapE(P88 L) | >16 | 4 | 0.25 | |
| V67-38 | 127 weeks | respiratory | CAS + POS | 2.87 ± 0.02 | 6.25 ± 0.01 | HapE(P88 L) | >16 | 4 | 0.25 | |
| P3 | V094-15 | 20 Feb 2010 | subcutaneous abscess | — | 2.77 ± 0.02 | 4.125 ± 0.02 | CYP51A(TR46/Y121F/T289A) | 1 | >16 | 0.25 |
| V094-16 | 20 Feb 2010 | subcutaneous abscess | — | 2.76 ± 0.02 | 7.375 ± 0.01 | CYP51A(TR46/Y121F/T289A) | 0.5 | >16 | 0.25 | |
| P4 | V186-81 | 3 Sep 2015 | sfenoid | — | 2.65 ± 0.01 | 6.625 ± 0.01 | NC | 0.25 | 0.25 | 0.063 |
| V187-02 | 3 Sep 2015 | sfenoid | — | — | 3.75 ± 0.02 | NC | — | — | — | |
| P5 | V148-33 | 6 May 2013 | sputum | no antifungal | 2.52 ± 0.01 | 3.4 ± 0.01 | NC | 0.5 | 0.5 | 0.125 |
| V186-45 | 29 Aug 2015 | sputum | no antifungal | 2.52 ± 0.01 | 3.4 ± 0.01 | NC | 0.5 | 1 | 0.25 | |
| E1 | CBS 140053 | 0 week | agricultural field | — | 2.49 ± 0.02 | 3.125 ± 0.01 | NC | 0.125 | 0.5 | 0.016 |
| CBS 140053 D1-7 | 7 weeks | evolutionary lines | DIF | 2.53 ± 0.01 | 8.625 ± 0.03 | CYP51A(G138S) | 32 | 4 | 0.5 | |
| E3 | CBS 140053 D3-7A | 7 weeks | evolutionary lines | DIF | 2.46 ± 0.02 | 6.25 ± 0.03 | NC | 8 | 2 | 0.5 |
| CBS 140053 D3-7B | 7 weeks | evolutionary lines | DIF | 2.51 ± 0.01 | 6.125 ± 0.01 | NC | 8 | 1 | 0.5 | |
| E6 | CBS 140053 D6-7A | 7 weeks | evolutionary lines | DIF | 2.49 ± 0.01 | 3.125 ± 0.02 | NC | 8(50%)/16(50%) | 2 | 0.25 |
| CBS 140053 D6-7B | 7 weeks | evolutionary lines | DIF | 2.47 ± 0.02 | 6.25 ± 0.01 | NC | 8 | 2 | 0.5 | |
aCAS, caspofungin; DIF, difenoconazole; ITR, itraconazole; L-AMB, liposomal amphotericin B; POS, posaconazole; VOR, voriconazole.
bMIC was determined four times for each isolate, most replicates showed consistence within replicates. There is one exception in E6, half showed 8 and another half showed 16. Resistance is indicated in italics (clinical breakpoints for resistance are MIC greater than 0.25 mg l−1 for POS and greater than 2 mg l−1 for ITR and, VOR).
cBAL, bronchoalveolar lavage.
dAmino acid changes in CYP51A and HapE; NC, no changes both on CYP51A and HapE.