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. 2020 May;63(5):430-436.
doi: 10.1111/myc.13064. Epub 2020 Mar 13.

First azole-resistant Aspergillus fumigatus isolates with the environmental TR46 /Y121F/T289A mutation in Iran

Fatemeh Ahangarkani  1   2 , Ynze Puts  2 , Mojtaba Nabili  3 , Sadegh Khodavaisy  4 , Maryam Moazeni  5   6 , Zahra Salehi  7 , Melika Laal Kargar  7 , Hamid Badali  5   6   8 , Jacques F Meis  2   9
Affiliations

First azole-resistant Aspergillus fumigatus isolates with the environmental TR46 /Y121F/T289A mutation in Iran

Fatemeh Ahangarkani et al. Mycoses. 2020 May.

Abstract

Background: Azole resistance in Aspergillus fumigatus is an emerging problem and reported from all continents. As triazole antifungals are the mainstay of therapy in the management of invasive aspergillosis, azole-resistant A fumigatus has become a major medical concern and with complicated clinical management.

Objective: Screening of environmental presence of azole-resistant A fumigatus in Iran.

Methods: Compost from Northern Iran, collected between 2017 and 2018, was screened for the presence of azole-resistant A fumigatus with azole-containing agar. Phenotypic MICs were obtained from selected, molecularly confirmed isolates. cyp51A gene sequencing and genotyping of azole-resistant isolates were done.

Results: Among 300 compost samples, three A fumigatus isolates had high voriconazole MICs (≥16 mg/L) and harboured the TR46 /Y121F/T289A mutation in the cyp51A gene. Microsatellite typing of these isolates showed that two strains had the same allele across all nine examined microsatellite loci and were genotypically related to Indian azole-resistant strains. The other isolate had a different genotype.

Conclusion: This is the first report of A fumigatus with TR46 /Y121F/T289A mutation from the region. Monitoring and surveillance of antifungal susceptibility of clinical A fumigatus is warranted in Iran and elsewhere in the region.

Keywords: Aspergillus fumigatus; TR34/L98H; TR46/Y121F/T289A; azole resistance; compost.

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Conflict of interest statement

JFM received grants from Pulmozyme and F2G. He has been a consultant to Scynexis and received speaker's fees from United Medical, TEVA and Gilead Sciences. The other authors report no conflicts of interest.

Figures

Figure 1
Figure 1
Minimum‐spanning tree showing the genetic relationship of A fumigatus genotypes harbouring TR46/Y121F/T289A mutation in cyp51A allele. Genotypic relationship of three Iranian isolates is illustrated by arrows
See this image and copyright information in PMC

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References

    1. Verweij PE, Chowdhary A, Melchers WJ, Meis JF. Azole resistance in Aspergillus fumigatus: Can we retain the clinical use of mold‐active antifungal azoles? Clin Infect Dis. 2016;62:362‐368. - PMC - PubMed
    1. Meis JF, Chowdhary A, Rhodes JL, Fisher MC, Verweij PE. Clinical implications of globally emerging azole resistance in Aspergillus fumigatus . Philos Trans R Soc Lond B Biol Sci. 2016;371:20150460. - PMC - PubMed
    1. Lestrade PPA, Meis JF, Melchers WJG, Verweij PE. Triazole resistance in Aspergillus fumigatus: recent insights and challenges for patient management. Clin Microbiol Infect. 2019;25:799‐806. - PubMed
    1. Chowdhary A, Kathuria S, Xu J, Meis JF. Emergence of azole‐resistant Aspergillus fumigatus strains due to agricultural azole use creates an increasing threat to human health. PLoS Pathog. 2013;9:e1003633. - PMC - PubMed
    1. Zhang J, Snelders E, Zwaan BJ, et al. A novel environmental azole resistance mutation in Aspergillus fumigatus and a possible role of sexual reproduction in its emergence. MBio. 2017;8:e00791‐e817. - PMC - PubMed