In vivo emergence of Aspergillus terreus with reduced azole susceptibility and a Cyp51a M217I alteration.
Azole resistance in Aspergillus terreus isolates was explored. Twenty related (MB) and 6 unrelated A. terreus isolates were included. CYP51A sequencing and RAPD genotyping was performed. Five MB isolates were itraconazole susceptible, whereas the minimum inhibitory concentrations (MICs) for 15 MB isolates were elevated (1-2 mg/L). Voriconazole and posaconazole MICs were 0.5-4 and 0.06-0.5 mg/L, respectively, for MB isolates but 0.25-0.5 and <0.03-0.06 mg/L, respectively, for controls. Sequencing identified a Cyp51Ap M217I alteration in all 15 isolates with elevated itraconazole MICs. Genotyping showed that 18 of 20 MB isolates were identical and unique, suggesting endogenous origin. In conclusion, itraconazole resistance in A. terreus was linked to an M217I Cyp51A alteration.
Mycology Unit, Department of Microbiological Surveillance and Research, Statens Serum Institut, Austria. maca@ssi.dk
Maiken C
MC
Arendrup
Rasmus H
RH
Jensen
Katharina
K
Grif
Marianne
M
Skov
Tacjana
T
Pressler
Helle K
HK
Johansen
Cornelia
C
Lass-Flörl
D000935:Antifungal Agents / Q000494:pharmacology*; D001230:Aspergillus / Q000145:classification* / Q000187:drug effects*; D001393:Azoles / Q000494:pharmacology*; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics / Q000378:metabolism*; D004271:DNA, Fungal / Q000235:genetics; D026141:Drug Resistance, Multiple, Fungal / Q000235:genetics*; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism*; D015966:Gene Expression Regulation, Fungal; D005838:Genotype; D006801:Humans; D017964:Itraconazole / Q000494:pharmacology; D008826:Microbial Sensitivity Tests; D009154:Mutation
D000935:Antifungal Agents; D001393:Azoles; D004271:DNA, Fungal; D005656:Fungal Proteins; D017964:Itraconazole; D003577:Cytochrome P-450 Enzyme System; C465526:cytochrome P-450 CYP51A, Aspergillus