Dataset Information

The Molecular Mechanism of Perillaldehyde Inducing Cell Death in Aspergillus flavus by Inhibiting Energy Metabolism Revealed by Transcriptome Sequencing.

ABSTRACT: Perillaldehyde (PAE), an essential oil in Perilla plants, serves as a safe flavor ingredient in foods, and shows an effectively antifungal activity. Reactive oxygen species (ROS) accumulation in Aspergillus flavus plays a critical role in initiating a metacaspase-dependent apoptosis. However, the reason for ROS accumulation in A. flavus is not yet clear. Using transcriptome sequencing of A. flavus treated with different concentrations of PAE, our data showed that the ROS accumulation might have been as a result of an inhibition of energy metabolism with less production of reducing power. By means of GO and KEGG enrichment analysis, we screened four key pathways, which were divided into two distinct groups: a downregulated group that was made up of the glycolysis and pentose phosphate pathway, and an upregulated group that consisted of MAPK signaling pathway and GSH metabolism pathway. The inhibition of dehydrogenase gene expression in two glycometabolism pathways might play a crucial role in antifungal mechanism of PAE. Also, in our present study, we systematically showed a gene interaction network of how genes of four subsets are effected by PAE stress on glycometabolism, oxidant damage repair, and cell cycle control. This research may contribute to explaining an intrinsic antifungal mechanism of PAE against A. flavus.

SUBMITTER: Pan C

PROVIDER: S-EPMC7073185 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature

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The Molecular Mechanism of Perillaldehyde Inducing Cell Death in Aspergillus flavus by Inhibiting Energy Metabolism Revealed by Transcriptome Sequencing.

Pan Chao C Li Yong-Xin YX Yang Kunlong K Famous Erhunmwunsee E Ma Yan Y He Xiaona X Geng Qingru Q Liu Man M Tian Jun J Tian Jun J

International journal of molecular sciences 20200223 4

Perillaldehyde (PAE), an essential oil in Perilla plants, serves as a safe flavor ingredient in foods, and shows an effectively antifungal activity. Reactive oxygen species (ROS) accumulation in Aspergillus flavus plays a critical role in initiating a metacaspase-dependent apoptosis. However, the reason for ROS accumulation in A. flavus is not yet clear. Using transcriptome sequencing of A. flavus treated with different concentrations of PAE, our data showed that the ROS acc ...[more]

PMID: 32102190

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Project description:Dimethyl sulfoxide (DSMO) is a simple molecule widely used because of its great solvating ability, but this solvent also has little-known biological effects, especially on fungi. Aspergillus flavus is a notorious pathogenic fungus which may contaminate a large variety of crops worldwide by producing aflatoxins, endangering at the same time food safety and international trade. The aim of this study was to characterize the effect of DMSO on A. flavus including developmental parameters such as germination and sporulation, as well as its transcriptome profile using high-throughput RNA-sequencing assay and its impact on secondary metabolism (SM). After DMSO exposure, A. flavus displayed depigmented conidia in a dose-dependent manner. The four-day exposition of cultures to two doses of DMSO, chosen on the basis of depigmentation intensity (35 mM "low" and 282 mM "high"), led to no significant impact on fungal growth, germination or sporulation. However, transcriptomic data analysis showed that 4891 genes were differentially regulated in response to DMSO (46% of studied transcripts). A total of 4650 genes were specifically regulated in response to the highest dose of DMSO, while only 19 genes were modulated upon exposure to the lowest dose. Secondary metabolites clusters genes were widely affected by the DMSO, with 91% of clusters impacted at the highest dose. Among these, aflatoxins, cyclopiazonic acid and ustiloxin B clusters were totally under-expressed. The genes belonging to the AFB1 cluster were the most negatively modulated ones, the two doses leading to 63% and 100% inhibition of the AFB1 production, respectively. The SM analysis also showed the disappearance of ustiloxin B and a 10-fold reduction of cyclopiazonic acid level when A. flavus was treated by the higher DMSO dose. In conclusion, the present study showed that DMSO impacted widely A. flavus' transcriptome, including secondary metabolism gene clusters with the aflatoxins at the head of down-regulated ones. The solvent also inhibits conidial pigmentation, which could illustrate common regulatory mechanisms between aflatoxins and fungal pigment pathways. Because of its effect on major metabolites synthesis, DMSO should not be used as solvent especially in studies testing anti-aflatoxinogenic compounds.

Project description:Purpose:The purpose of this study was to investigate the therapeutic effect of perillaldehyde (PAE) on Aspergillus fumigatus (A. fumigatus) keratitis. Methods:Human corneal epithelial cells (HCECs) were pretreated with PAE and stimulated with A. fumigatus mycelium. C57BL/6 mice were infected with A. fumigatus and treated with or without PAE 1 day after infection. Clinical scores, PCR, ELISA, and Western blotting were used to detect the expression of pro-inflammatory mediators, dendritic cell-associated c-type lectin-1 (Dectin-1), nuclear factor (erythroid-derived 2) like 2 (Nrf2), and heme oxygenase (HO-1). Nrf2 expression in HCECs pretreated with PAE was observed by immunofluorescence. NIMP-R14 protein expression and localization in mouse corneas were observed by immunofluorescence staining after treatment with PAE. Corneal colony counting, time-kill tests, and mycelial transformation inhibition tests were used to evaluate the antifungal effect of PAE. Results:C57BL/6 mice treated with PAE at 1 day after infection had a lower clinical score and decreased IL-1?, TNF-?, IL-6, Dectin-1, and MPO levels. PAE treatment significantly reduced neutrophil recruitments to the corneal stroma. Compared with the DMSO-treated group, PAE treatment significantly decreased mRNA and protein levels of pro-inflammatory cytokines and Dectin-1 in HCECs. PAE pretreatment before A. fumigatus stimulation obviously elevated the mRNA and protein levels of components of the Nrf2/HO-1 axis. HCECs pretreated with PAE before infection showed a weakened ability to inhibit inflammation in the presence of brusatol (BT; an Nrf2 inhibitor) or ZnPP (an HO-1 inhibitor). PAE treatment significantly reduced the fungal load of C57BL/6 mouse corneas and inhibited fungal growth in vitro. Conclusions:These data proved that PAE may ameliorate A. fumigatus keratitis by activating the Nrf2/HO-1 signaling pathway and inhibiting the Dectin-1 mediated inflammatory response and neutrophil recruitment. Furthermore, PAE exerts direct fungicidal activity on A. fumigatus.

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Dataset Information

The Molecular Mechanism of Perillaldehyde Inducing Cell Death in Aspergillus flavus by Inhibiting Energy Metabolism Revealed by Transcriptome Sequencing.

Publications

The Molecular Mechanism of Perillaldehyde Inducing Cell Death in <i>Aspergillus flavus</i> by Inhibiting Energy Metabolism Revealed by Transcriptome Sequencing.

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