Carbon catabolite repression gene creA regulates morphology, aflatoxin biosynthesis and virulence in Aspergillus flavus

Fasoyin, Opemipo Esther; Wang, Bin; Qiu, Mengguang; Han, Xiao; Chung, Kwong T.; Wang, Shihua

doi:10.1016/j.fgb.2018.04.008

Cited by 69 publications

(68 citation statements)

References 50 publications

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“…Indeed we found that all 19 assigned aflatoxin genes were significantly downregulated in a two independent ∆creA mutants compared with WT ( Figure 5). These results were consistent with the loss of aflatoxin synthesis in the deletion of creA in another strain of A. flavus, CA14 [18]. GA treated samples (P08) compared with the untreated samples (P).…”

Section: Genes In a Flavus In Response To Gasupporting

confidence: 85%

“…To confirm the hypothesis that CreA was involved in aflatoxin gene regulation, we deleted creA in A. flavus and the ∆creA mutants were unable to produce the mycotoxin. The qRT-PCR result showed that the expression of the aflatoxin genes were significantly down regulated in the ∆creA mutants compared to WT, which is consistent with an identical role for this protein in aflatoxin biosynthesis in another strain of A. flavus, CA14 [18]. In A. flavus, GprC was considered as carbon sensing [38] which may mediate the expression of carbon utilization genes.…”

Section: Discussionsupporting

confidence: 66%

“…Gallic acid (GA), a constituent in the pellicle of Tulare walnut, has shown potent inhibitory activity toward aflatoxin biosynthesis [16], but the mechanism of GA inhibition of aflatoxin formation has not been studied. We present here our finding that GA significantly inhibited the expression of farB gene, which controls the activity of peroxisomal fatty acid β oxidation [17], and of the carbon repression regulator encoding gene creA which has recently been found involved in aflatoxin synthesis [18]. Simultaneously, the expression of almost all assigned genes in the aflatoxin biosynthesis cluster was significantly downregulated by 0.8% (w/v) GA treatment.…”

Section: Introductionmentioning

confidence: 61%

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The Antioxidant Gallic Acid Inhibits Aflatoxin Formation in <em>Aspergillus flavus</em> by Modulating Transcription Factors FarB and CreA

Zhao¹,

Zhi²,

Li³

et al. 2018

Preprint

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Aflatoxin biosynthesis is correlated with oxidative stress and is proposed to function as a secondary defense mechanism to redundant intracellular reactive oxygen species (ROS). We find that the antioxidant gallic acid inhibits aflatoxin formation and growth in A. flavus in a dose-dependent manner. Global expression analysis (RNA-Seq) of gallic acid treated A. flavus showed that 0.8% (w/v) gallic acid revealed two possible routes of aflatoxin inhibition. Gallic acid significantly inhibited the expression of farB, encoding a transcription factor that participates in peroxisomal fatty acid β oxidation, a fundamental contributor to aflatoxin production. Secondly, the carbon repression regulator encoding gene creA was significantly down regulated by gallic acid treatment. CreA is necessary for aflatoxin synthesis and aflatoxin biosynthesis genes were significantly downregulated in DcreA mutants. In addition, the results of antioxidant enzyme activities and the lipid oxidation levels coupled with RNA-Seq data of antioxidant genes indicated that gallic acid may reduce oxidative stress through the glutathione- and thioredoxin-dependent systems in A. flavus.

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Section: Genes In a Flavus In Response To Gasupporting

confidence: 85%

Section: Discussionsupporting

confidence: 66%

Section: Introductionmentioning

confidence: 61%

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The Antioxidant Gallic Acid Inhibits Aflatoxin Formation in <em>Aspergillus flavus</em> by Modulating Transcription Factors FarB and CreA

Zhao¹,

Zhi²,

Li³

et al. 2018

Preprint

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“…Homologous recombination strategy was used to generate the A. flavus AflO deletion mutant as previously described (Fasoyin et al, 2018). Three fragments (upstream, downstream of AflO and Pyrg selectable marker) were amplified with specific primers (see Table S1), and then overlapped by a fusion PCR .…”

Section: Construction Of Aflo Deletion and Point Mutantsmentioning

confidence: 99%

Lysine acetylation contributes to development, aflatoxin biosynthesis and pathogenicity in Aspergillus flavus

Guang

Yue

Ren

et al. 2019

Environmental Microbiology

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Summary Aspergillus flavus is a pathogenic fungus that produces carcinogenic aflatoxins, posing a great threat to crops, animals and humans. Lysine acetylation is one of the most important reversible post‐translational modifications and plays a vital regulatory role in various cellular processes. However, current information on the extent and function of lysine acetylation and aflatoxin biosynthesis in A. flavus is limited. Here, a global acetylome analysis of A. flavus was performed by peptide pre‐fractionation, pan‐acetylation antibody enrichment and liquid chromatography–mass spectrometry. A total of 1313 high‐confidence acetylation sites in 727 acetylated proteins were identified in A. flavus. These acetylation proteins are widely involved in glycolysis/gluconeogenesis, pentose phosphate pathway, citric acid cycle and aflatoxin biosynthesis. AflO (O‐methyltransferase), a key enzyme in aflatoxin biosynthesis, was found to be acetylated at K241 and K384. Deletion of aflO not only impaired conidial and sclerotial developments, but also dramatically suppressed aflatoxin production and pathogenicity of A. flavus. Further site‐specific mutations showed that lysine acetylation of AflO could also result in defects in development, aflatoxin production and pathogenicity, suggesting that acetylation plays a vital role in the regulation of the enzymatic activity of AflO in A. flavus. Our findings provide evidence for the involvement of lysine acetylation in various biological processes in A. flavus and facilitating in the elucidation of metabolic networks.

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“…This implied that the WT strain may be able to utilize proline better than glutamine, and this was evident in the slightly increased colony size and AFB1 quantity in the proline-containing medium. On the other hand, despite the ability of proline to be utilized as both nitrogen and carbon source, it could not rescue the lack of the function of areA in AFB1 production, and this may be due to carbon catabolite repression induced by glucose [46]. It has been previously shown in A. nidulans that AreA is not sufficient for the utilization of proline, and the presence of CreA hinders the action of the element required for its full utilization [47].…”

Section: Discussionmentioning

confidence: 95%

Regulation of Morphology, Aflatoxin Production, and Virulence of Aspergillus flavus by the Major Nitrogen Regulatory Gene areA

Fasoyin

Yang

Qiu

et al. 2019

Toxins

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Aspergillus flavus is a renowned plant, animal and human pathogen. areA is a global nitrogen regulatory gene of the GATA transcription factor family, shown to be the major nitrogen regulator. In this study, we identified areA in A. flavus and studied its function. The AreA protein contained a signatory zinc finger domain, which is extremely conserved across fungal species. Gene deletion (∆areA) and over-expression (OE::areA) strains were constructed by homologous recombination to elucidate the role of areA in A. flavus. The ∆areA strain was unable to efficiently utilize secondary nitrogen sources for growth of A. flavus, and it had poorly developed conidiophores, when observed on complete medium, resulting in the production of significantly less conidia than the wild-type strain (WT). Aflatoxin B1 (AFB1) production was reduced in ∆areA compared with the WT strain in most conditions tested, and ∆areA had impaired virulence in peanut seeds. areA also played important roles in the sensitivity of A. flavus to osmotic, cell wall and oxidative stresses. Hence, areA was found to be important for the growth, aflatoxin production and pathogenicity of A. flavus. This work sheds light on the function of areA in the regulation of the nitrogen metabolism of A. flavus, and consequently aims at providing new ways for controlling the crossover pathogen, A. flavus. Key Contribution:The GATA transcription factor and major nitrogen regulator AreA, was shown to regulate nitrogen metabolism and aflatoxin B1 production in A. flavus.

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Carbon catabolite repression gene creA regulates morphology, aflatoxin biosynthesis and virulence in Aspergillus flavus

Cited by 69 publications

References 50 publications

The Antioxidant Gallic Acid Inhibits Aflatoxin Formation in <em>Aspergillus flavus</em> by Modulating Transcription Factors FarB and CreA

The Antioxidant Gallic Acid Inhibits Aflatoxin Formation in <em>Aspergillus flavus</em> by Modulating Transcription Factors FarB and CreA

Lysine acetylation contributes to development, aflatoxin biosynthesis and pathogenicity in Aspergillus flavus

Regulation of Morphology, Aflatoxin Production, and Virulence of Aspergillus flavus by the Major Nitrogen Regulatory Gene areA

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