Abstract
Azole-resistance in Aspergillus fumigatus is a worldwide medical concern complicating the management of aspergillosis (IA). Herein, we report the clonal spread of environmental triazole resistant A. fumigatus isolates in Iran. In this study, 63 A. fumigatus isolates were collected from 300 compost samples plated on Sabouraud dextrose agar supplemented with itraconazole (ITR) and voriconazole (VOR). Forty-four isolates had the TR34/L98H mutation and three isolates a TR46/Y121F/T289A resistance mechanism, while two isolates harbored a M172V substitution in cyp51A. Fourteen azole resistant isolates had no mutations in cyp51A. We found that 41 out of 44 A. fumigatus strains with the TR34/L98H mutation, isolated from compost in 13 different Iranian cities, shared the same allele across all nine examined microsatellite loci. Clonal expansion of triazole resistant A. fumigatus in this study emphasizes the importance of establishing antifungal resistance surveillance studies to monitor clinical Aspergillus isolates in Iran, as well as screening for azole resistance in environmental A. fumigatus isolates.
Highlights
Aspergillus fumigatus is the most common agent of various forms of aspergillosis, including allergic bronchopulmonary aspergillosis (ABPA), chronic pulmonary aspergillosis (CPA), aspergilloma, and invasive aspergillosis (IA) [1]
A. fumigatus with the TR34 /L98H mutation isolated from environmental and clinical samples have been reported earlier in Iran, and we recently reported the occurrence of TR46 /Y121F/T289A mutations in the cyp51A gene in A. fumigatus isolates from compost [12,13,14,15,16,17,18]
Exploring the mechanisms of resistance in these isolates by sequencing cyp51A and its promoter region showed that 44 isolates harbored the TR34 /L98H mutation, three isolates the TR46 /Y121F/T289A
Summary
Aspergillus fumigatus is the most common agent of various forms of aspergillosis, including allergic bronchopulmonary aspergillosis (ABPA), chronic pulmonary aspergillosis (CPA), aspergilloma, and invasive aspergillosis (IA) [1]. Azole resistance in A. fumigatus is mainly linked to cyp51A-mediated resistance mechanism, such as a 34-basepair (bp) sequence tandem repeat (TR34 ) in the promoter region of the cyp51A gene, in combination with a L98H substitution and a 46 bp tandem repeat (TR46 ) in the cyp51A promoter in combination with two amino acid changes (Y121F and T289A) in the CYP51A protein (TR46 /Y121F/T289A) [9] Isolates carrying these mutations exhibit a pan-azole resistant phenotype that can develop through long-term treatment with azole antifungals in the clinical setting or extensive exposure of the fungus to azole compounds in the environment [10,11].
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