Fungicides induced triazole-resistance in Aspergillus fumigatus associated with mutations of TR46/Y121F/T289A and its appearance in agricultural fields

Azole resistance in Aspergillus fumigatus is a growing public health problem. The sources of this resistance have been gained much attention. The present study was conducted to assess if resistant strain of A. fumigatus and its associated mutations in cyp51A could be induced by triazole fungicides and whether the resistant strain of A. fumigatus exist in agricultural fields. The results indicated that the resistance in A. fumigatus with mutations of TR46/Y121F/T289A, A284T, G448S and P222Q could be induced by agricultural triazoles (epoxiconazole, tebuconazole, propiconazole, hexaconazole, and metconazole). TR46/Y121F/T289A was the most common mutation in the induced resistant strain of A. fumigatus. A total of 144 soil samples were collected from different greenhouses for vegetables and fruits in Zhejiang, China. Among them, 2 voriconazole-resistant strains (No. 15 and 44) harboring the mutation of TR46/Y121F/T289A and 1 itraconazole-resistant strain (No. 51) harboring the mutation of TR34/L98H/S297T/F495I were isolated and identified. This implies that resistant strain of A. fumigatus has already distributed at least in 5.8% of the greenhouses. These findings might imply that there is a direct link between the agricultural use of triazoles and the appearance of the resistance in A. fumigatus to triazole medicals and its associated mutations in cyp51A.