Carr Paul D, Tuckwell Danny, Hey Peter M, Simon Laurence, d'Enfert Christophe, Birch Mike, Oliver Jason D, Bromley Michael J
F2G Limited, Lankro Way, Eccles, Manchester, United Kingdom.
Eukaryot Cell. 2010 Mar;9(3):438-48. doi: 10.1128/EC.00324-09. Epub 2010 Jan 22.
Genes that are essential for viability represent potential targets for the development of anti-infective agents. However, relatively few have been determined in the filamentous fungal pathogen Aspergillus fumigatus. A novel solution employing parasexual genetics coupled with transposon mutagenesis using the Fusarium oxysporum transposon impala had previously enabled the identification of 20 essential genes from A. fumigatus; however, further use of this system required a better understanding of the mode of action of the transposon itself. Examination of a range of conditions indicated that impala is activated by prolonged exposure to low temperatures. This newly identified property was then harnessed to identify 96 loci that are critical for viability in A. fumigatus, including genes required for RNA metabolism, organelle organization, protein transport, ribosome biogenesis, and transcription, as well as a number of noncoding RNAs. A number of these genes represent potential targets for much-needed novel antifungal drugs.
对生存至关重要的基因是开发抗感染药物的潜在靶点。然而,在丝状真菌病原体烟曲霉中确定的此类基因相对较少。一种新的方法,即利用准性遗传学结合使用尖孢镰刀菌转座子黑斑羚进行转座子诱变,此前已从烟曲霉中鉴定出20个必需基因;然而,进一步使用该系统需要更好地了解转座子本身的作用模式。对一系列条件的研究表明,黑斑羚转座子在长时间暴露于低温时被激活。然后利用这一新发现的特性来鉴定96个对烟曲霉生存至关重要的基因座,包括RNA代谢、细胞器组织、蛋白质运输、核糖体生物合成和转录所需的基因,以及一些非编码RNA。其中许多基因是急需的新型抗真菌药物的潜在靶点。