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转录因子SomA是人类病原体烟曲霉黏附、发育和毒力所必需的。

Transcription Factor SomA Is Required for Adhesion, Development and Virulence of the Human Pathogen Aspergillus fumigatus.

作者信息

Lin Chi-Jan, Sasse Christoph, Gerke Jennifer, Valerius Oliver, Irmer Henriette, Frauendorf Holm, Heinekamp Thorsten, Straßburger Maria, Tran Van Tuan, Herzog Britta, Braus-Stromeyer Susanna A, Braus Gerhard H

机构信息

Department of Molecular Microbiology and Genetics, Institute of Microbiology & Genetics, Georg-August-University Göttingen, Göttingen, Germany.

Institute for Organic and Biomolecular Chemsitry, Georg-August-University Göttingen, Göttingen, Germany.

出版信息

PLoS Pathog. 2015 Nov 3;11(11):e1005205. doi: 10.1371/journal.ppat.1005205. eCollection 2015.

Abstract

The transcription factor Flo8/Som1 controls filamentous growth in Saccharomyces cerevisiae and virulence in the plant pathogen Magnaporthe oryzae. Flo8/Som1 includes a characteristic N-terminal LUG/LUH-Flo8-single-stranded DNA binding (LUFS) domain and is activated by the cAMP dependent protein kinase A signaling pathway. Heterologous SomA from Aspergillus fumigatus rescued in yeast flo8 mutant strains several phenotypes including adhesion or flocculation in haploids and pseudohyphal growth in diploids, respectively. A. fumigatus SomA acts similarly to yeast Flo8 on the promoter of FLO11 fused with reporter gene (LacZ) in S. cerevisiae. FLO11 expression in yeast requires an activator complex including Flo8 and Mfg1. Furthermore, SomA physically interacts with PtaB, which is related to yeast Mfg1. Loss of the somA gene in A. fumigatus resulted in a slow growth phenotype and a block in asexual development. Only aerial hyphae without further differentiation could be formed. The deletion phenotype was verified by a conditional expression of somA using the inducible Tet-on system. A adherence assay with the conditional somA expression strain indicated that SomA is required for biofilm formation. A ptaB deletion strain showed a similar phenotype supporting that the SomA/PtaB complex controls A. fumigatus biofilm formation. Transcriptional analysis showed that SomA regulates expression of genes for several transcription factors which control conidiation or adhesion of A. fumigatus. Infection assays with fertilized chicken eggs as well as with mice revealed that SomA is required for pathogenicity. These data corroborate a complex control function of SomA acting as a central factor of the transcriptional network, which connects adhesion, spore formation and virulence in the opportunistic human pathogen A. fumigatus.

摘要

转录因子Flo8/Som1控制酿酒酵母中的丝状生长以及植物病原体稻瘟病菌中的毒力。Flo8/Som1包含一个特征性的N端LUG/LUH-Flo8-单链DNA结合(LUFS)结构域,并由cAMP依赖性蛋白激酶A信号通路激活。烟曲霉的异源SomA在酵母flo8突变菌株中挽救了几种表型,分别包括单倍体中的黏附或絮凝以及二倍体中的假菌丝生长。在酿酒酵母中,烟曲霉SomA在与报告基因(LacZ)融合的FLO11启动子上的作用与酵母Flo8相似。酵母中FLO11的表达需要一个包括Flo8和Mfg1的激活复合物。此外,SomA与PtaB发生物理相互作用,PtaB与酵母Mfg1相关。烟曲霉中somA基因的缺失导致生长缓慢的表型以及无性发育受阻。只能形成没有进一步分化的气生菌丝。使用可诱导的Tet-on系统对somA进行条件性表达,验证了缺失表型。对条件性somA表达菌株进行的黏附试验表明,生物膜形成需要SomA。ptaB缺失菌株表现出类似的表型,支持SomA/PtaB复合物控制烟曲霉生物膜形成。转录分析表明,SomA调节控制烟曲霉分生孢子形成或黏附的几种转录因子的基因表达。用受精鸡蛋以及小鼠进行的感染试验表明,致病性需要SomA。这些数据证实了SomA作为转录网络的核心因子具有复杂的控制功能,该转录网络连接了机会性人类病原体烟曲霉中的黏附、孢子形成和毒力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/46c8/4631450/f016009103b2/ppat.1005205.g001.jpg

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