| Aspergillus fumigatus,a common airborne fungal pathogen,is the principal aetiological agent in Invasive aspergillosis.However,azole resistance has been frequently found in clinic isolates of A.fumigatus and become a public health menace.Some studies indicated that the applications of azole fungicides in agriculture might be one of the sources of azole resistance in A.fumigatus..In this study,imidazoles fungicide imazalil and triazole fungicide triticonazole as inducing substrate,to test its feasibility of induced triazole medicine resistant A.fumigatus.After a series of 8-day exposures to Imazalil with progressive increasing concentrations ranging from 1 to 16 mg/L,the data on the A.fumigatus with changes in MICs to voriconazole or itraconazole.4 of 14 A.fumigatus sensitive strains showed high resistance to voriconazole,and sequence analysis of cyp51A gene of them exhibited the same mutation of TR46/Y121F/T289A,resulting in amino acid changes of tyrosine to phenylalanine at codon 121 and threonine to alanine at codon 289,coupled with a tandem repeat of a 46-base pair sequence in the promoter region.It is reported that the voriconazole-resistance of A.fumigatus is coused by mutation of TR46/Y121F/T289A.2 of 14 A.fumigatus sensitive strains showed high resistance to itraconazole,and the sequence analysis of cyp51A gene of one of them exhibited the mutation of TR34/L98H/S297T/F4951.However,the genetic changes of S297T and F495I have no significant effect on the phenotype but moderate the phenotype of the voriconazole resistance only in the presence of TR34/L98H.The sequence analysis of cyp51A gene of the other one of them exhibited the mutation of Y433N.The results demonstrate that the temporary resistance in A.fumigatus to itraconazole and the mutation of Y433N might be unrelated,and there is no metabolic resistance in A.fumigatus which with Y433N in cyp51A.And after a series of 8-day exposures to triticonazole with progressive increasing concentrations ranging from 1 to 16 mg/L,the data on the A.fumigatus with changes in MICs to voriconazole or itraconazole.3 of 14 A.fumigatus sensitive strains showed high resistance to voriconazole,and sequence analysis of cyp51A gene of them exhibited the same mutation of TR46/Y121F/T289A,which coused voriconazole-resistance of A.fumigatus.2 of 14 Af.umigatus sensitive strains showed high resistance to itraconazole,and sequence analysis of cyp51A gene of them exhibited the same mutation of TR34/L98H/S297T/F495I,which coused itraconazole-resistance of A.fumigatus.The half-life of triticonazole in soil is 35.99 days,and triticonazole might produce a effect on triazole fungicide sensibility of A.fumigatus.2 itraconazole resistancet Af.umigatus were isolated from the soil sample which was polluted with triticonazole,and sequence analysis of cyp51A gene of them exhibited the same mutation of Y433N.As a chiral pesticide,the 50%effective concentration(EC50)value of S-triticonazole to Gibberella zeae is 2.34 mg/L,and the EC50 value of R-triticonazole is 1.53 mg/L.The control efficiency of R-triticonazole to Gibberella zeae is better than S-triticonazole.The toxicity of R-triticonazole to A.fumigatus is better than S-triticonazole as well.Furthermore,after a series of 8-day exposures to S-triticonazole or R-triticonazole with progressive increasing concentrations ranging from 1 to 16 mg/L,the possibility of producing triazole resistant A.fumigatus by R-triticonazole was lower than that of S-triticonazole.There are 3 of 14 triazole resistant A.fumigatus strains produced after induced by S-triticonazole,but only 1 of 14 triazole resistant A.fumigatus strains produced after induced by R-triticonazole.Triazole resistant A.fumigatus with the same mutation of Y433N in cyp51A ware found in both in induction test and the soil exposure test.However,there is no direct evidence to prove therelationship between the mutation of Y433N and triazole resistant A.fumigatus,the possible mechanism remains to be explored. |
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