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mtfA转录因子基因控制着机会性人类病原体烟曲霉的形态发生、gliotoxin产生及毒力。

The mtfA transcription factor gene controls morphogenesis, gliotoxin production, and virulence in the opportunistic human pathogen Aspergillus fumigatus.

作者信息

Smith Timothy D, Calvo Ana M

机构信息

Department of Biological Sciences, Northern Illinois University, Dekalb, Illinois, USA.

Department of Biological Sciences, Northern Illinois University, Dekalb, Illinois, USA

出版信息

Eukaryot Cell. 2014 Jun;13(6):766-75. doi: 10.1128/EC.00075-14. Epub 2014 Apr 11.

Abstract

Aspergillus fumigatus is the leading causative agent of invasive aspergillosis (IA). The number of cases is on the rise, with mortality rates as high as 90% among immunocompromised patients. Molecular genetic studies in A. fumigatus could provide novel targets to potentially set the basis for antifungal therapies. In the current study, we investigated the role of the transcription factor gene mtfA in A. fumigatus. Our results revealed that mtfA plays a role in the growth and development of the fungus. Deletion or overexpression of mtfA leads to a slight reduction in colony growth, as well as a reduction in conidiation levels, in the overexpression strain compared to the wild-type strain. Furthermore, production of the secondary metabolite gliotoxin increased when mtfA was overexpressed, coinciding with an increase in the transcription levels of the gliotoxin genes gliZ and gliP with respect to the wild type. In addition, our study showed that mtfA is also necessary for normal protease activity in A. fumigatus; deletion of mtfA resulted in a reduction of protease activity compared to wild-type levels. Importantly, the absence of mtfA caused a decrease in virulence in the Galleria mellonella infection model, indicating that mtfA is necessary for A. fumigatus wild-type pathogenesis.

摘要

烟曲霉是侵袭性曲霉病(IA)的主要病原体。病例数量呈上升趋势,免疫功能低下患者的死亡率高达90%。烟曲霉的分子遗传学研究可为抗真菌治疗提供新的潜在靶点。在本研究中,我们调查了转录因子基因mtfA在烟曲霉中的作用。我们的结果表明,mtfA在真菌的生长和发育中发挥作用。与野生型菌株相比,mtfA的缺失或过表达导致菌落生长略有减少,以及过表达菌株中分生孢子形成水平降低。此外,当mtfA过表达时,次生代谢产物Gliotoxin的产量增加,这与Gliotoxin基因gliZ和gliP相对于野生型的转录水平增加相一致。此外,我们的研究表明,mtfA对于烟曲霉中的正常蛋白酶活性也是必需的;与野生型水平相比,mtfA的缺失导致蛋白酶活性降低。重要的是,mtfA的缺失导致在黄粉虫感染模型中毒力下降,表明mtfA是烟曲霉野生型致病所必需的。

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