CAJ | 학술논문

目的：构建烟曲霉体外诱导伊曲康唑耐药株，初步探讨与CYP 51A基因的相关性。方法通过含有伊曲康唑的固体培养基对烟曲霉进行梯度浓度体外诱导耐药，微量液基稀释法测定诱导株对伊曲康唑的敏感性；提取诱导株基因组，扩增唑类药物靶酶CYP 51A基因，进行测序和序列分析。结果诱导获得8株烟曲霉体外诱导株，其中6株对伊曲康唑表现出耐药性。耐药株唑类药物靶酶CYP 51A基因发生G54(G54R, G54E)和L98H的点突变。结论伊曲康唑体外梯度浓度诱导是获得烟曲霉伊曲康唑耐药株的有效方法；烟曲霉对伊曲康唑抗真菌药物的耐药性可能与唑类药物靶点基因CYP 51A的点突变相关。
목적：구건연곡매체외유도이곡강서내약주，초보탐토여CYP 51A기인적상관성。방법통과함유이곡강서적고체배양기대연곡매진행제도농도체외유도내약，미량액기희석법측정유도주대이곡강서적민감성；제취유도주기인조，확증서류약물파매CYP 51A기인，진행측서화서렬분석。결과유도획득8주연곡매체외유도주，기중6주대이곡강서표현출내약성。내약주서류약물파매CYP 51A기인발생G54(G54R, G54E)화L98H적점돌변。결론이곡강서체외제도농도유도시획득연곡매이곡강서내약주적유효방법；연곡매대이곡강서항진균약물적내약성가능여서류약물파점기인CYP 51A적점돌변상관。
Objective To obtain in vitro itraconazole-resistant strains of Aspergillus fumigatus and explore its relationship with CYP 51A gene. Methods Wild type strain of Aspergillus fumigatus was serially transferred to agar medium containing itraconazole of gradually increased concentration in vitro. The in vitro susceptibility of induced strains was determined by broth microdilution assay. The genomes of itraconazole-resistant mutant strains were extracted, then the azole drugs target enzyme gene CYP 51A was ampliifed, sequenced and analyzed. Results Eight induced strains of Aspergillus fumigatus in vitro were obtained, and six strains shown resistance to itraconazole. Azole drugs target enzyme gene CYP 51A of itraconazole-resistant strains occurs G54 (G54R, G54E) and L98H point mutations. Conclusions Itraconazole-resistant strains of Aspergillus fumigatus can be induced in vitro by concentration gradient. Point mutations of azole antifungal drug target enzyme gene CYP 51A maybe associate with Aspergillus fumigatus resistance to itraconazole.