关键词: Alternative therapies Aspergillus nidulans Phenolic compounds Quorum-sensing RNAseq Tyrosol

Mesh : Antifungal Agents / pharmacology metabolism Transcriptome Aspergillus nidulans Glutathione / genetics metabolism pharmacology Carbon / metabolism Gene Expression Regulation, Fungal Fungal Proteins / genetics metabolism Phenylethyl Alcohol / analogs & derivatives

来  源:   DOI:10.1016/j.funbio.2024.01.003

Abstract:
Although tyrosol is a quorum-sensing molecule of Candida species, it has antifungal activity at supraphysiological concentrations. Here, we studied the effect of tyrosol on the physiology and genome-wide transcription of Aspergillus nidulans to gain insight into the background of the antifungal activity of this compound. Tyrosol efficiently reduced germination of conidia and the growth on various carbon sources at a concentration of 35 mM. The growth inhibition was fungistatic rather than fungicide on glucose and was accompanied with downregulation of 2199 genes related to e.g. mitotic cell cycle, glycolysis, nitrate and sulphate assimilation, chitin biosynthesis, and upregulation of 2250 genes involved in e.g. lipid catabolism, amino acid degradation and lactose utilization. Tyrosol treatment also upregulated genes encoding glutathione-S-transferases (GSTs), increased specific GST activities and the glutathione (GSH) content of the cells, suggesting that A. nidulans can detoxify tyrosol in a GSH-dependent manner even though this process was weak. Tyrosol did not induce oxidative stress in this species, but upregulated \"response to nutrient levels\", \"regulation of nitrogen utilization\", \"carbon catabolite activation of transcription\" and \"autophagy\" genes. Tyrosol may have disturbed the regulation and orchestration of cellular metabolism, leading to impaired use of nutrients, which resulted in growth reduction.
摘要:
尽管酪醇是念珠菌物种的群体感应分子,它在超生理浓度下具有抗真菌活性。这里,我们研究了酪醇对构巢曲霉的生理和全基因组转录的影响,以深入了解该化合物的抗真菌活性背景。Tyrosol在35mM的浓度下有效地减少了分生孢子的萌发和在各种碳源上的生长。对葡萄糖的生长抑制是真菌抑制的,而不是杀真菌剂,并伴随着与有丝分裂细胞周期相关的2199基因的下调,糖酵解,硝酸盐和硫酸盐同化,几丁质生物合成,以及与例如脂质分解代谢有关的2250个基因的上调,氨基酸降解和乳糖利用。酪氨酸溶胶处理还上调编码谷胱甘肽-S-转移酶(GSTs)的基因,细胞的特定GST活性和谷胱甘肽(GSH)含量增加,这表明,牛乳杆菌可以以依赖GSH的方式解毒酪醇,即使这个过程很弱。Tyrosol在该物种中没有诱导氧化应激,但上调了“对营养水平的反应”,“氮利用法规”,“碳分解代谢物转录激活”和“自噬”基因。Tyrosol可能扰乱了细胞代谢的调节和协调,导致营养素使用受损,这导致了增长的减少。
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