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First azole-resistant Aspergillus fumigatus isolates with the environmental TR46 /Y121F/T289A mutation in Iran
Fatemeh Ahangarkani1,2, Ynze Puts2, Mojtaba Nabili3
1Student Research Committee, Mazandaran University of Medical Sciences, Sari, Iran.
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.
Insights
Azole-resistant Aspergillus fumigatus, a growing threat to invasive aspergillosis treatment, was detected in Iranian compost. This finding highlights the need for antifungal resistance surveillance in the region.
Area of Science:
- Medical Mycology
- Antimicrobial Resistance
- Environmental Microbiology
Background:
- Azole resistance in Aspergillus fumigatus is a significant global health concern.
- Triazole antifungals are crucial for treating invasive aspergillosis, making azole-resistant strains a clinical challenge.
- Emerging azole resistance necessitates environmental monitoring to understand transmission dynamics.
Purpose of the Study:
- To investigate the environmental prevalence of azole-resistant Aspergillus fumigatus in Iran.
- To screen compost samples for the presence of resistant fungal strains.
- To characterize the genetic basis of resistance in detected isolates.
Main Methods:
- Screening of 300 compost samples from Northern Iran (2017-2018) using azole-containing agar.
- Determination of phenotypic Minimum Inhibitory Concentrations (MICs) for confirmed isolates.
- Sequencing of the cyp51A gene and microsatellite typing for genotypic analysis.
Main Results:
- Three Aspergillus fumigatus isolates exhibited high voriconazole MICs (≥16 mg/L).
- These isolates carried the TR46/Y121F/T289A mutation in the cyp51A gene.
- Two isolates were genotypically related to Indian azole-resistant strains, while one had a distinct genotype.
Conclusions:
- This study reports the first detection of Aspergillus fumigatus with the TR46/Y121F/T289A mutation in Iran.
- Environmental surveillance identified azole-resistant strains, indicating a potential public health risk.
- Ongoing monitoring of antifungal susceptibility in clinical Aspergillus fumigatus isolates from Iran and the region is recommended.

