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Volume 25, Number 3—March 2019
Dispatch

In Vivo Selection of a Unique Tandem Repeat Mediated Azole Resistance Mechanism (TR120) in Aspergillus fumigatus cyp51A, Denmark

Rasmus K. HareComments to Author , Jan B. Gertsen, Karen M.T. Astvad, Kristine B. Degn, Anders Løkke, Marc Stegger, Paal S. Andersen, Lise Kristensen, and Maiken C. ArendrupComments to Author 
Author affiliations: Statens Serum Institut, Copenhagen, Denmark (R.K. Hare, K.M.T. Astvad, M. Stegger, P.S. Andersen, M.C. Arendrup); Åarhus University Hospital, Åarhus, Denmark (J.B. Gertsen, K.B. Degn, A. Løkke, L. Kristensen); Rigshospitalet, Copenhagen (M.C. Arendrup); University of Copenhagen, Copenhagen (M.C. Arendrup)

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Table

Aspergillus fumigatus strain characteristics, antimicrobial susceptibility, and molecular data, Denmark, 2013*

Isolate no. EUCAST-based susceptibility MICs, mg/L
 Sanger sequencing: Cyp51A profile§ STRAf assay genotyping data:† 2A-2B-2C-3A-3B-3C-4A-4B-4C WGS data:‡ SNP differences compared with P-1
VRZ ITZ POS
P-1 1 0.5 0.125 F46Y/M172V/E427K 10–13–10–17–13–8–7–5–6 0
P-2 4 16 0.5 TR120/F46Y/M172V/E427K 10–13–10–17–13–8–7–5–6 NA
P-3 4 >16 0.5 TR120/F46Y/M172V/E427K 10–13–10–17–13–8–7–5–6 41
SSI-5197 1 1 0.125 F46Y/M172V/E427K 10-15-10-28-13-11-7-5-6 4,968
SSI-7413 0.5 0.25 0.125 WT 21–25–19–28–12–6–20–10–8 105,900
Af293 (13) 1 0.5 0.06 F46Y/M172V/N248T/D255E/E427K 26–18–18–46–21–23–11–10–8 102,727
SSI-5946 4 >16 0.5 TR34/L98H 20–21–12–84–10–7–8–9–10 108,901
SSI-5717 >4 0.5 0.25 TR46/Y121F/T289A 26–21–16–32–9–10–8–14–10 108,882

*ITZ, itraconazole; NA, not available; POS, posaconazole; SNP, single-nucleotide polymorphism; STRAf, short tandem repeat Aspergillus fumigatus; VRZ, voriconazole (isavuconazole MICs were equivalent, data not shown); WGS, whole-genome sequencing; WT, wild-type.
†STRAf genotyping was performed as previously described (3). Underlined STRAf markers are shared with P-1.
‡Reference genome coverage ranged from 88.5% to 90.93%. Sequencing depth based on all assembled contigs >1,000 bp ranged from 57.2× to 80.7×; 71.1× for P-1; and 66.3× for P-3.
§TR34: GAATCACGCGGTCCGGATGTGTGCTGAGCCGAAT, TR46: AGTTGTCTAGAATCACGCGGTCCGGATGTGTGCTGAGCCGAATGAA,
TR120: TTCTCCTCTAGAAAAAACTCATGAGTGAATAATCGCAGCACCACTCCAGAGTTGTCTAGAATCACGCGGTCCGGATGTGTGCTGAGCCGAATGAAAGTTGCCTAATTACTAAGGTGTAGT. GenBank accession numbers are MG972983 with TR120 and MG972984 without TR120.

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