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Published on: April 19, 2017
Activity of Azole and Non-Azole Substances Against Aspergillus fumigatus in Clinical and Environmental Samples to
Isabella Sanseverino1, Diletta Scaccabarozzi1, Marcos Cuesta Sanz1
1European Commission, Joint Research Centre (JRC), Via E. Fermi 2749, 21027 Ispra, Italy.
Abstract:
Aspergillus fumigatus is a common fungus which has gained attention due to its resistance to azole compounds, substances used in both medical and agricultural settings. One of the genetic alterations responsible for this resistance is the mutation TR34/L98H in the cyp51A gene. The aim of this study was to understand the impact of azoles and non-azoles on Aspergillus fumigatus. By examining clinical samples, soil samples, and compost material, this research aims to provide insights into the susceptibility of these strains to antifungal substances. To deepen our understanding of the factors potentially involved in antifungal resistance, we combined in vitro studies of sixteen compounds against Aspergillus fumigatus with results from the sequencing of the cyp51 gene. We observed that compounds generally displayed a similar pattern activity against wild-type Aspergillus fumigatus. Non-azoles, except Pyrisoxazole and Amisulbrom, did not show any activity against Aspergillus fumigatus, while azole compounds displayed differential activity against the fungus, except for Tetraconazole. For the mutant strains, a generally similar activity was observed in both clinical and environmental samples, likely due to the same mutation in all the isolates. The implications of these findings may be relevant for better understanding the relationship between Aspergillus fumigatus and its ability to develop resistance to antifungal substances.
Insights
This study investigated antifungal resistance in Aspergillus fumigatus, finding azoles show varied activity while most non-azoles are ineffective. Understanding this resistance is crucial for developing new antifungal treatments.
Area of Science:
- Medical Mycology
- Antimicrobial Resistance
- Fungal Genetics
Background:
- Aspergillus fumigatus exhibits azole resistance, a significant concern in medicine and agriculture.
- The TR34/L98H mutation in the cyp51A gene is a key genetic driver of this resistance.
Purpose of the Study:
- To evaluate the impact of azole and non-azole compounds on Aspergillus fumigatus.
- To investigate antifungal susceptibility in clinical and environmental isolates.
Main Methods:
- In vitro testing of sixteen compounds against Aspergillus fumigatus.
- Sequencing of the cyp51 gene in clinical and environmental isolates.
Main Results:
- Azole compounds demonstrated differential activity against wild-type Aspergillus fumigatus, with Tetraconazole showing less effect.
- Most non-azole compounds lacked activity, with exceptions like Pyrisoxazole and Amisulbrom.
- Mutant strains from clinical and environmental sources showed similar antifungal susceptibility patterns.
Conclusions:
- The TR34/L98H mutation influences antifungal resistance similarly across different Aspergillus fumigatus sample types.
- Findings contribute to understanding the complex relationship between Aspergillus fumigatus and antifungal resistance mechanisms.
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