Table 1.
The 44 known mutation sites previously reported to be associated with triazole resistance and results of the Fisher’s Exact tests using 122 A. fumigatus strains with known itraconazole and voriconazole MICs.
| Gene | Codon | Amino Acid Change | Chromosome—Position (bp) | Fisher’s Exact Test (p-Values), MIC ≥ 2 mg/L | Fisher’s Exact Test (p-Values), MIC ≥ 4 mg/L | References | ||
|---|---|---|---|---|---|---|---|---|
| Itraconazole | Pan-Azole | Itraconazole | Pan-Azole | |||||
|
cyp51A
(AFUA_4G06890) |
N22 | NA 1 | [30] | |||||
| * F46 | Y | CHR 4—1,781,686 | 4.50 × 10−3 | 3.54 × 10−2 | 4.50 × 10−3 | 2.96 × 10−2 | [30] | |
| S52 | NA 1 | [31] | ||||||
| G54 | V, E | CHR 4—1,781,662 | 1.55 × 10−1 | 1.00 | 1.55 × 10−1 | 1.00 | [30] | |
| W, R | CHR 4—1,781,663 | 8.16 × 10−2 | 2.72 × 10−2 | 8.16 × 10−2 | 8.90 × 10−3 | |||
| Q88 | NA 1 | [31] | ||||||
| L98 | H | CHR 4—1,781,459 | 1.19 × 10−5 | 3.33 × 10−6 | 1.19 × 10−5 | 1.47 × 10−5 | [30] | |
| V101 | NA 1 | [31] | ||||||
| Y121 | F | CHR 4—1,781,390 | 2.81 × 10−1 | 2.42 × 10−1 | 2.81 × 10−1 | 9.71 × 10−2 | [30] | |
| N125 | NA 1 | [31] | ||||||
| G138 | C | CHR 4—1,781,340 | 8.09 × 10−2 | 1.00 | 8.09 × 10−2 | 1.00 | [31] | |
| Q141 | NA 1 | [31] | ||||||
| H147 | Y | CHR 4—1,781,313 | 1.00 | 1.00 | 1.00 | 1.00 | [31] | |
| F165 | NA 1 | [30] | ||||||
| * M172 | NA 1 | [30] | ||||||
| P216 | L | CHR 4—1,781,105 | 5.23 × 10−1 | 4.95 × 10−1 | 5.23 × 10−1 | 2.19 × 10−1 | [30] | |
| F219 | S | CHR 4—1,781,096 | 2.91 × 10−1 | 2.44 × 10−1 | 2.91 × 10−1 | 1.04 × 10−1 | [30] | |
| M220 | I | CHR 4—1,781,092 | 1.00 | 1.00 | 1.00 | 1.00 | [30] | |
| V | CHR 4—1,781,094 | 2.87 × 10−1 | 1.00 | 2.87 × 10−1 | 1.00 | |||
| M236 | NA 1 | [31] | ||||||
| * N248 | NA 1 | [30] | ||||||
| * D255 | E | CHR 4—1,780,987 | 6.30 × 10−1 | 1.00 | 6.30 × 10−1 | 1.00 | [30] | |
| D262 | NA 1 | [30] | ||||||
| A284 | NA 1 | [30] | ||||||
| T289 | A | CHR 4—1,780,887 | 2.91 × 10−1 | 2.44 × 10−1 | 2.91 × 10−1 | 1.04 × 10−1 | [30] | |
| S297 | T | CHR 4—1,780,863 | 5.26 × 10−1 | 1.00 | 5.26 × 10−1 | 1.00 | [31] | |
| P394 | NA 1 | [31] | ||||||
| * E427 | K | CHR 4 - 1,780,473 |
5.00 × 10−3 | 3.69 × 10−2 | 5.00 × 10−3 | 3.11 × 10−2 | [30] | |
| Y431 | NA 1 | [30] | ||||||
| G432 | NA 1 | [30] | ||||||
| G434 | NA 1 | [30] | ||||||
| T440 | NA 1 | [30] | ||||||
| G448 | S | CHR 4—1,780,410 | 1.00 | 1.00 | 1.00 | 4.71 × 10−1 | [30] | |
| N479 | NA 1 | [30] | ||||||
| Y491 | NA 1 | [30] | ||||||
| F495 | I | CHR 4—1,780,269 | 5.22 × 10−1 | 1.00 | 5.22 × 10−1 | 1.00 | [31] | |
|
cyp51B
(AFUA_7G03740) |
G457 | NA 1 | [32] | |||||
|
hapE
(AFUA_6G05300) |
P88 | NA 1 | [30] | |||||
|
hmg1
(AFUA_2G03700) |
F262 | NA 1 | [33] | |||||
| S305 | P | CHR 2—985,959 | 5.22 × 10−1 | 4.95 × 10−1 | 5.22 × 10−1 | 2.14 × 10−1 | [33] | |
| P309 | L | CHR 2—985,972 | 1.00 | 1.00 | 1.00 | 1.00 | [33] | |
| I412 | T, S | CHR 2—986,281 | 1.56 × 10−1 | 1.17 × 10−1 | 1.56 × 10−1 | 4.34 × 10−2 | [33] | |
|
erg6
(AFUA_4G03630) |
A350 | NA 1 | [34] | |||||
|
cox10
(AFUA_4G08340) |
R243 | NA 1 | [35] | |||||
| AFUA_7G01960 | L167 | Stop Gained | CHR 7—531,582 | 1.00 | 1.00 | 1.00 | 4.66 × 10−1 | [36] |
| AFUA_2G10600 | E180 | D | CHR 2—2,714,188 | 6.39 × 10−2 | 2.33 × 10−2 | 6.39 × 10−2 | 8.79 × 10−3 | [37] |
* The reference strain Af293 contains the cyp51A mutations F46Y, M172V, N248T, D255E, and E427K. 1 The mutation sites were not found in the soft filtered genotype file, prior to multiallelic site removal.