烟曲霉Afssn3缺失菌株对伊曲康唑耐药的转录组学分析

Transcriptomic Analysis of Afssn 3 deficientAspergillus Fumigatus Strains on Itraconazole Resistance

在烟曲霉Afssn3缺失菌株和野生型对照菌株中分别加入伊曲康唑进行处理,并应用Illumina二代测序技术对两组样本进行转录组学测序和生物信息学分析.结果发现:经伊曲康唑处理后,Afssn3敲除菌株类固醇生物合成通路中cyp51A(erg11A)、erg24B、mes01(erg25)、smt1(erg6)、sc5dl(erg3)等基因表达显著上调,外排泵ABC转运蛋白相关的mdr4基因也显著上调;烟曲霉Afssn3敲除后,菌株可通过上调麦角固醇合成通路的药靶基因cyp51A(erg11A)和药物外排泵的转录水平等导致耐药.该研究揭示了烟曲霉Afssn3基因敲除菌株和野生型对照菌株经伊曲康唑刺激后,会出现表达差异的信号通路和相应的基因.这为烟曲霉耐药分子调控机制的研究提供了新的线索和依据.

Itraconazole was added to Afssn 3 deficient Aspergillus fumigatus strain and the wild type control strain,respectively,and the transcriptomic sequencing and bioinformatics analysis of the two groups of samples were carried out by Illumina second generation sequencing technology.After itraconazole treatment,the expression of cyp51A(erg11A),erg24B,mes01(erg25),smt1(erg6),sc5dl(erg3)and other genes in the steroid biosynthesis pathway of the Afssn 3 knockout strain were significantly up regulated,the mdr 4 gene related to efflux pump ABC transporter was also significantly up regulated.In addition,after knockout of Afssn3 in Aspergillus fumigatus,the strain can induce drug resistance by up regulating the drug target gene cyp51A(erg11A)of the ergosterol synthesis pathway and the transcription level of the drug efflux pump.This study reveals that the Aspergillus fumigatus Afssn3 gene knockout strain and the wild type control strain express different signal pathways and corresponding genes after stimulation with itraconazole,which is expected to provide new clues and basis for the study of the molecular regulation mechanism of resistance of Aspergillus fumigatus.