Role of VeA-Dependent Genes and Proteins in Mycotoxin Production and Development

VeA 依赖性基因和蛋白质在霉菌毒素产生和发展中的作用

• 批准号: 8367019
• 负责人: ANA M CALVO-BYRD
• 金额: $ 35.47万
• 依托单位: NORTHERN ILLINOIS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-02-01 至 2016-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8367019
• 关键词: Acremonium; Affect; Aflatoxins; Anabolism; Animals; Antibiotics; Appearance; Aspergillus; Aspergillus flavus; Aspergillus fumigatus; Aspergillus nidulans; Biological Models; Development; Food Chain; Fruit; Fungi Model; Fusarium; Gene Proteins; Genes; Goals; Gossypium; Grant; Health; Homologous Gene; Human; Metabolism; Modeling; Molecular; Morphogenesis; Mutagenesis; Mutation; Mycotoxins; Nature; Neurospora crassa; Nuts; Oils; Pathway interactions; Phenotype; Plants; Production; Proteins; Proteomics; Regulation; Regulator Genes; Reproduction spores; Research; Resistance; Role; Seeds; Sexual Development; Signal Pathway; Sorghum; Sterigmatocystin; Structure; Work; asexual; economic impact; fungus; genetic element; health economics; insight; mutant; novel; pathogen; prevent

DESCRIPTION (provided by applicant): Aspergillus spp. mycotoxins infect corn, cotton, sorghum and nuts. Controlling mycotoxin biosynthesis or fungal development would decrease its devastating health and economic impact. Because signaling pathways tend to be conserved in Aspergillus spp, the model system Aspergillus nidulans is used to study regulation of mycotoxin production and morphological development. Aspergillus spp. produce resistant structures: sclerotia in Aspergillus flavus and Aspergillus parasiticus and fruiting bodies called cleistothecia in A. nidulans. Molecular studies over the control of cleistothecial or sclerotial development are limited. Only a few regulatory genes are known. We found that deletion of the veA gene blocks mycotoxin production as well as the formation of resistant structures in A. nidulans, A. flavus and A. parasiticus. We also found that morphological development and secondary metabolism is also controlled by this global regulator across genera. The VeA protein is a fungal-specific promising target for a control strategy; however, it does not present homology to previously described proteins. The main goal of our previous AREA grant was to further characterize the regulatory mechanism through which VeA controls mycotoxin biosynthesis and morphogenesis, in the model system, A. nidulans. For that we have a) Identified VeA interacting proteins, and b) obtained several suppressor mutants in a deletion veA strain for the identification of the genetic elements downstream from veA involved in mycotoxin production. We successfully carried out these objectives. Following a proteomics approach we have identified VeA-interacting proteins. Also our mutagenesis approach, applied according to the previous aim 2, resulted in several revertant mutants, two of them are fully characterized as outlined in the previous AREA grant. In the current AREA we propose: Aim1: to characterize novel VeA interacting proteins, and Aim 2: to characterize revertant mutants and the genes affected by the inflicted mutations. Because of the conserved nature of fungal regulatory networks across species and the fact that VeA has only been found in fungi, a control strategy involving VeA may be effective against mycotoxin contamination by Aspergillus spp. and against other plant and animal pathogens. PUBLIC HEALTH RELEVANCE: This is a renewal of a previous AREA grant study on the mechanism of action of VeA, a fungal global regulator that controls the biosynthesis of secondary metabolites, such as potent carcinogenic mycotoxins, as well as fungal development. The fact that VeA is unique to fungi and it is conserved in many fungi, makes VeA a valuable possible target to control fungal pathogens and the production of deleterious mycotoxins that constitute an important health threat.

描述(申请人提供)：曲霉属。霉菌毒素侵染玉米、棉花、高粱和坚果。控制霉菌毒素的生物合成或真菌发展将减少其破坏性的健康和经济影响。由于信号通路在曲霉属中往往是保守的，因此利用模型系统研究霉菌毒素的产生和形态发育的调控。曲霉属(Aspergilla spp.)产生抗性结构：在黄曲霉和寄生曲霉中产生菌核，在球果曲霉中产生称为闭囊菌的子实体。关于控制闭锁或菌核发育的分子研究有限。只有几个调控基因是已知的。我们发现，Vea基因的缺失阻碍了根结线虫、黄曲霉和寄生曲霉真菌毒素的产生和抗性结构的形成。我们还发现，形态发育和次生代谢也受到这个跨属的全局调控因子的控制。VEA蛋白是真菌特异性的有希望的控制策略的靶标；然而，它与先前描述的蛋白质不存在同源性。我们以前的面积资助的主要目标是在模式系统中进一步描述VEA控制真菌毒素生物合成和形态发生的调控机制。为此，我们已经鉴定了VEA相互作用蛋白，以及b)在缺失VEA菌株中获得了几个抑制突变体，用于鉴定VEA下游参与真菌毒素生产的遗传元件。我们成功地实现了这些目标。按照蛋白质组学的方法，我们已经确定了VEA相互作用的蛋白质。此外，我们的诱变方法，根据先前的目标2，导致了几个回复突变，其中两个完全特征，如前面的区域拨款概述。在当前领域，我们提出：AIM1：鉴定新的VEA相互作用蛋白，目标2：鉴定突变株和受突变影响的基因。由于真菌调控网络在物种间的保守性，以及VEA只在真菌中发现的事实，涉及VEA的控制策略可能有效地防止曲霉毒素的污染。以及对抗其他动植物病原体。 与公共卫生相关：这是先前关于VEA作用机制的面积拨款研究的更新，VEA是一种真菌全球调节器，控制次生代谢物的生物合成，如强致癌霉菌毒素，以及真菌发育。VEA是真菌所特有的，在许多真菌中都是保守的，这使得VEA成为控制真菌病原体和有害真菌毒素产生的有价值的可能目标，这些毒素构成了对健康的重要威胁。

项目成果

cpsA regulates mycotoxin production, morphogenesis and cell wall biosynthesis in the fungus Aspergillus nidulans.

• DOI: 10.1111/mmi.13682
• 发表时间: 2017-07
• 期刊: Molecular microbiology
• 影响因子: 3.6
• 作者: Feng X;Ramamoorthy V;Pandit SS;Prieto A;Espeso EA;Calvo AM
• 通讯作者: Calvo AM

The putative C2H2 transcription factor MtfA is a novel regulator of secondary metabolism and morphogenesis in Aspergillus nidulans.

• DOI: 10.1371/journal.pone.0074122
• 发表时间: 2013
• 期刊: PloS one
• 影响因子: 3.7
• 作者: Ramamoorthy V;Dhingra S;Kincaid A;Shantappa S;Feng X;Calvo AM
• 通讯作者: Calvo AM

Cross-talk between light and glucose regulation controls toxin production and morphogenesis in Aspergillus nidulans.

• DOI: 10.1016/j.fgb.2010.08.007
• 发表时间: 2010-12
• 期刊: FUNGAL GENETICS AND BIOLOGY
• 影响因子: 3
• 作者: Atoui, A.;Kastner, C.;Larey, C. M.;Thokala, R.;Etxebeste, O.;Espeso, E. A.;Fischer, R.;Calvo, A. M.
• 通讯作者: Calvo, A. M.