TABLE 3.
FKS sequencing resultsa
Anidula MIC (μg/ml) | Caspo MIC (μg/ml) | Mica MIC (μg/ml) | Flucon MIC (μg/ml) | Gene and hot spot region(s) |
|
---|---|---|---|---|---|
FKS1 HS1 | FKS2 HS1 | ||||
0.125 | 0.25 | 0.008 | 128 | WT | WT |
0.015 | 0.25 | 0.008 | 32 | WT | WT |
0.03 | 0.5 | 0.008 | 4 | WT | WT |
0.016 | 0.25 | 0.008 | 4 | WT | WT |
0.125 | 0.25 | 0.016 | 1 | WT | WT |
0.016 | 0.5 | 0.016 | 64 | WT | WT |
0.03 | 0.25 | 0.016 | 8 | WT | WT |
0.125 | 0.25 | 0.016 | 8 | WT | WT |
0.03 | 0.25 | 0.03 | 4 | WT | WT |
0.25 | 0.125 | 0.03 | 128 | WT | WT |
0.125 | 0.25 | 0.03 | 128 | WT | WT |
0.125 | 0.25 | 0.03 | 4 | WT | WT |
0.125 | 0.25 | 0.03 | 4 | WT | WT |
0.06 | 0.25 | 0.06 | 4 | WT | WT |
0.125 | 0.25 | 0.06 | 64 | WT | WT |
0.125 | 0.5 | 0.06 | 64 | WT | WT |
0.25 | 0.125 | 0.06 | 4 | WT | WT |
0.25 | 0.125 | 0.06 | 4 | F L I L S L R Y P | WT |
0.5 | 0.25 | 0.125 | 2 | WT | F L I L F L R D P |
0.03 | 0.25 | 0.125 | 128 | WT | WT |
0.5 | 0.5 | 0.125 | 64 | F L I L P L R D P | WT |
0.5 | 0.125 | 0.125 | 64 | F L I L P L R D P | WT |
0.125 | 0.5 | 0.125 | 16 | WT | WT |
0.125 | 0.125 | 0.125 | 8 | WT | WT |
0.06 | 0.06 | 0.125 | 4 | WT | WT |
0.5 | 0.5 | 0.125 | 4 | WT | WT |
2 | 2 | 0.25 | 0.25 | WT | F L I L S L R D H |
1 | 0.5 | 0.25 | 256 | WT | Y L I L S L R D P |
1 | 2 | 0.25 | 256 | WT | Y L I L S L R D P |
0.06 | 0.125 | 0.25 | 64 | F L I L S L G D P | WT |
2 | 2 | 0.25 | 64 | WT | F L I L F L R D P |
1 | 1 | 0.25 | 32 | WT | S L I L S L R D P |
0.06 | 0.125 | 0.25 | 32 | F L I L S L G D P | WT |
1 | 1 | 0.25 | 16 | F L I L S L R V P | WT |
1 | 1 | 0.25 | 8 | WT | Y L I L S L R D P |
0.06 | 0.125 | 0.25 | 8 | WT | WT |
0.06 | 0.06 | 0.25 | 8 | WT | WT |
0.03 | 0.06 | 0.25 | 4 | I634V | WT |
0.03 | 0.03 | 0.25 | 4 | WT | WT |
1 | 2 | 0.25 | 4 | WT | Y L I L S L R D P |
0.5 | 1 | 0.25 | 4 | WT | Y L I L S L R D P |
2 | 2 | 0.5 | 2 | WT | F L I L P L R D P |
0.5 | 0.25 | 0.5 | 1 | F L I L S L G D P | F L I L S L R V P |
0.25 | 0.25 | 0.5 | 128 | F L I L S L G D P | WT |
1 | 1 | 0.5 | 128 | WT | delF658 |
0.03 | 0.06 | 0.5 | 8 | WT | WT |
0.125 | 0.125 | 0.5 | 4 | F L I L P L R D P | F L I L S L R V P |
0.03 | 0.03 | 0.5 | 4 | WT | WT |
1 | 0.5 | 1 | 4 | F L I L P L R D P | WT |
0.25 | 0.5 | 1 | 2 | F L I L S L G D P | WT |
2 | 8 | 1 | 256 | F L I L P L R D P | WT |
2 | 4 | 1 | 64 | F L I L P L R D P | F L I L S L R V P |
2 | 16 | 1 | 64 | WT | F L I L P L R D P |
1 | 4 | 1 | 64 | WT | F L I L P L R D P |
2 | 2 | 1 | 4 | WT | WT |
2 | 4 | 2 | 4 | WT | F L I L P L R D P |
0.5 | 1 | 2 | 4 | WT | F L I L P L R D P |
4 | 8 | 2 | 128 | WT | F L I L P L R D P |
2 | 1 | 2 | 128 | WT | F L I L P L R D P |
2 | >16 | 2 | 128 | WT | F L I L P L R D P |
2 | >16 | 2 | 64 | WT | F L I L P L R D P |
4 | >16 | 2 | 16 | WT | F L I L P L R D P |
4 | >16 | 2 | 16 | F L I L P L R D P | WT |
4 | 16 | 2 | 8 | WT | F L I L P L R D P |
4 | >16 | 2 | 8 | WT | delF658 |
1 | 16 | 2 | 8 | WT | F L I L P L R D P |
4 | >16 | 2 | 8 | WT | F L I L P L R D P |
2 | 16 | 2 | 4 | WT | F L I L P L R D P |
4 | >16 | 4 | 4 | WT | F L I L P L R D P |
2 | 8 | 4 | 4 | WT | F L I L P L R D P |
0.5 | 16 | 4 | 256 | WT | F L I L P L R D P |
2 | 16 | 4 | 128 | WT | F L I L P L R D P |
4 | >16 | 4 | 64 | WT | F L I L P L R D P |
2 | 16 | 4 | 32 | WT | F L I L P L R D P |
4 | 16 | 4 | 32 | WT | F L I L P L R D P |
Among the 77 isolates with at least one echinocandin MIC in the intermediate or resistant range, FKS sequencing identified 47 with FKS mutations. Three of the isolates had a mutation that was one amino acid outside the recognized hot spot region. All of the mutations were in FKS1 hot spot 1 or FKS2 hot spot 1. This includes 47/55 (85%) isolates that showed resistance to at least one echinocandin. Anidula, anidulafungin; Caspo, caspofungin; Mica, micafungin; Flucon, fluconazole; WT, wild type. Boldface indicates the amino acid that has been changed in the hot spot.