Yu Lu, Zhang Wenliang, Wang Lingling, Yang Jian, Liu Tao, Peng Junping, Leng Wenchuan, Chen Lihong, Li Ruoyu, Jin Qi
State Key Laboratory for Molecular Virology and Genetic Engineering, Chinese Center for Disease Control and Prevention, Beijing 100176, China.
Antimicrob Agents Chemother. 2007 Jan;51(1):144-53. doi: 10.1128/AAC.00755-06. Epub 2006 Oct 23.
Trichophyton rubrum is a pathogenic filamentous fungus of increasing medical concern. Two antifungal agents, ketoconazole (KTC) and amphotericin B (AMB), have specific activity against dermatophytes. To identify the mechanisms of action of KTC and AMB against T. rubrum, a cDNA microarray was constructed from the expressed sequence tags of the cDNA library from different developmental stages, and transcriptional profiles of the responses to KTC and AMB were determined. T. rubrum was exposed to subinhibitory concentrations of KTC and AMB for 12 h, and microarray analysis was used to examine gene transcription. KTC exposure induced transcription of genes involved in lipid, fatty acid, and sterol metabolism, including ERG11, ERG3, ERG25, ERG6, ERG26, ERG24, ERG4, CPO, INO1, DW700960, CPR, DW696584, DW406350, and ATG15. KTC also increased transcription of the multidrug resistance gene ABC1. AMB exposure increased transcription of genes involved in lipid, fatty acid, and sterol metabolism (DW696584, EB801458, IVD, DW694010, DW688343, DW684992), membrane transport (Git1, DW706156, DW684040, DMT, DW406136, CCH1, DW710650), and stress-related responses (HSP70, HSP104, GSS, AOX, EB801455, EB801702, TDH1, UBI4) but reduced transcription of genes involved in maintenance of cell wall integrity and signal transduction pathways (FKS1, SUN4, DW699324, GAS1, DW681613, SPS1, DW703091, STE7, DW703091, DW695308) and some ribosomal proteins. This is the first report of the use of microarray analysis to determine the effects of drug action in T. rubrum.
红色毛癣菌是一种日益引起医学关注的致病性丝状真菌。两种抗真菌药物，酮康唑（KTC）和两性霉素B（AMB），对皮肤癣菌具有特异性活性。为了确定KTC和AMB对红色毛癣菌的作用机制，利用来自不同发育阶段的cDNA文库的表达序列标签构建了一个cDNA微阵列，并测定了对KTC和AMB反应的转录谱。将红色毛癣菌暴露于亚抑制浓度的KTC和AMB中12小时，并用微阵列分析来检测基因转录。暴露于KTC诱导了参与脂质、脂肪酸和甾醇代谢的基因转录，包括ERG11、ERG3、ERG25、ERG6、ERG26、ERG24、ERG4、CPO、INO1、DW700960、CPR、DW696584、DW406350和ATG15。KTC还增加了多药耐药基因ABC1的转录。暴露于AMB增加了参与脂质、脂肪酸和甾醇代谢（DW696584、EB801458、IVD、DW694010、DW688343、DW684992）、膜转运（Git1、DW706156、DW684040、DMT、DW406136、CCH1、DW710650）和应激相关反应（HSP70、HSP104、GSS、AOX、EB801455、EB801702、TDH1、UBI4）的基因转录，但降低了参与细胞壁完整性维持和信号转导途径（FKS1、SUN4、DW699324、GAS1、DW681613、SPS1、DW703091、STE7、DW703091、DW695308）以及一些核糖体蛋白的基因转录。这是首次报道利用微阵列分析来确定药物作用对红色毛癣菌的影响。
