Department of Medical Parasitology and Mycology, Tehran University of Medical Sciences, Tehran, Iran.
Department of Medical Parasitology and Mycology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
J Mycol Med. 2020 Jun;30(2):100953. doi: 10.1016/j.mycmed.2020.100953. Epub 2020 Mar 26.
The present study was designed to discover novel biomarkers involved in voriconazole resistance in clinical isolates of Aspergillus flavus.
Two voriconazole non-wild-type and two voriconazole-wild-type A. flavus clinical isolates were selected to evaluate possible molecular mechanism involved in A. flavus resistance to voriconazole using the mutation assessment, Quantitative real- time PCR of cyp51A and cyp51C genes and complementary DNA- amplified fragment length polymorphism technique.
No mutations were seen in the cyp51A and cyp51C genes in voriconazole non-wild-type isolates compared to wild- type and reference strains. Regarding to mRNA expression results, no changes were observed in expression fold of cyp51A and cyp51C mRNA expression level in first non- wild- type isolate compared to wild-type isolate. For second isolate cyp51C mRNA expression level was down regulated (5.6 fold). The set of genes including ABC fatty acid transporter XM- 002375835 and aldehydereductase XM- 002376518 and three unknown functional genes were identified. Based on results, the over-expression of AKR1 and ABC fatty acid transporter in the voriconazole non- wild- type isolates suggests these genes could represent a novel molecular marker linked to the voriconazole resistance in A. flavus.
The results obtained in this study showed a novel finding as the authors identified AKR1 and ABC fatty acid transporter genes as possible voriconazole target genes in Iranian clinical isolates of A. flavus.
本研究旨在发现与黄曲霉临床分离株中伏立康唑耐药相关的新型生物标志物。
选择两株伏立康唑非野生型和两株伏立康唑野生型黄曲霉临床分离株，通过突变评估、cyp51A 和 cyp51C 基因定量实时 PCR 和 cDNA 扩增片段长度多态性技术，评估黄曲霉对伏立康唑耐药的可能分子机制。
与野生型和参考株相比，伏立康唑非野生型分离株中 cyp51A 和 cyp51C 基因未发现突变。关于 mRNA 表达结果，与野生型分离株相比，第一个非野生型分离株中 cyp51A 和 cyp51C mRNA 表达水平的表达倍数没有变化。对于第二个分离株，cyp51C mRNA 表达水平下调（5.6 倍）。鉴定出一组基因，包括 ABC 脂肪酸转运蛋白 XM-002375835 和醛脱氢酶 XM-002376518 以及三个未知功能基因。基于结果，伏立康唑非野生型分离株中 AKR1 和 ABC 脂肪酸转运蛋白的过表达表明这些基因可能代表与黄曲霉伏立康唑耐药相关的新型分子标记。
本研究结果表明，作者在伊朗黄曲霉临床分离株中发现 AKR1 和 ABC 脂肪酸转运蛋白基因可能是伏立康唑的靶基因，这是一个新的发现。
