VeA Is Associated with the Response to Oxidative Stress in the Aflatoxin Producer Aspergillus flavus

Baidya, Sachin; Duran, Rocio M.; Lohmar, Jessica M.; Harris-Coward, Pamela Y.; Cary, Jeffrey W.; Hong, Sung Yong; Roze, Ludmila V.; Linz, John E.; Calvo, Ana M.

doi:10.1128/ec.00099-14

Cited by 64 publications

(53 citation statements)

References 48 publications

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“…A recent study performed in A. fumigatus suggested that AtfB might be regulated by SakA pathway and also demonstrated that atfB expression was dosedependently increased by using different concentrations of the antifungal agent caspofungin (Pereira Silva et al, 2016). In paralell, AtfB was demonstrated to be positively regulated by VeA (Baidya et al, 2014). By contrast, in our study, atfB was over expressed while veA levels were decreased suggesting that other factors may influence atfB expression.…”

Section: Piperine Inhibits Afb1 Production and Modulates Bzip Transcrcontrasting

confidence: 93%

“…In A. flavus, veA is also necessary for oxidative stress tolerance since it controls genes intervening in the HOG (high-osmolarity glycerol) signaling pathway. Indeed, veA deletion resulted in decreased transcription levels of several genes intervening in stress response such as srrA, msnA or atfA (Baidya et al, 2014).…”

Section: Piperine Impacts Cellular Signaling Receptors and The Globalmentioning

confidence: 99%

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Piperine inhibits aflatoxin B1 production in Aspergillus flavus by modulating fungal oxidative stress response

Caceres

Khoury

Bailly

et al. 2017

Fungal Genetics and Biology

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Aspergillus flavus, a soil-borne pathogen, represents a danger for humans and animals since it produces the carcinogenic mycotoxin Aflatoxin B1 (AFB1). Approaches aiming the reduction of this fungal contaminant mainly involve chemicals that may also be toxic. Therefore, identification and characterization of natural antiaflatoxigenic products represents a sustainable alternative strategy. Piperine, a major component of black and long peppers, has been previously demonstrated as an AFB1-inhibitor; nevertheless its mechanism of action was yet to be elucidated. The aim of the present study was to evaluate piperine's molecular mechanism of action in A. flavus with a special focus on oxidative stress response. For that, the entire AFB1 gene cluster as well as a targeted gene-network coding for fungal stress response factors and cellular receptors were analyzed. In addition to this, fungal enzymatic activities were also characterized. We demonstrated that piperine inhibits aflatoxin production and fungal growth in a dose-dependent manner. Analysis of the gene cluster demonstrated that almost all genes participating in aflatoxin's biosynthetic pathway were down regulated. Exposure to piperine also resulted in decreased transcript levels of the global regulator veA together with an over-expression of genes coding for several basic leucine zipper (bZIP) transcription factors such as atfA, atfB and ap-1 and genes belonging to superoxide dismutase and catalase's families.Furthermore, this gene response was accompanied by a significant enhancement of Version postprintComment citer ce document :

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Section: Piperine Inhibits Afb1 Production and Modulates Bzip Transcrcontrasting

confidence: 93%

Section: Piperine Impacts Cellular Signaling Receptors and The Globalmentioning

confidence: 99%

Piperine inhibits aflatoxin B1 production in Aspergillus flavus by modulating fungal oxidative stress response

Caceres

Khoury

Bailly

et al. 2017

Fungal Genetics and Biology

View full text Add to dashboard Cite

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“…Treatment with BHA as also been shown to inhibit sclerotial differentiation in A. flavus . Oxidative stress responsive signaling mechanisms have been found to be involved in the regulation of aflatoxin production such as the stress responsive transcription factors AtfB, AP-1, and VeA (Reverberi et al, 2008; Sakamoto et al, 2008; Roze et al, 2011, 2013; Hong et al, 2013a,b; Baidya et al, 2014). Also, VeA along with VelB and LaeA form the Velvet protein complex to regulate both secondary metabolite production and reproductive development in A. flavus and other Aspergillus spp.…”

Section: Introductionmentioning

confidence: 99%

Responses of Aspergillus flavus to Oxidative Stress Are Related to Fungal Development Regulator, Antioxidant Enzyme, and Secondary Metabolite Biosynthetic Gene Expression

et al. 2016

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The infection of maize and peanut with Aspergillus flavus and subsequent contamination with aflatoxin pose a threat to global food safety and human health, and is exacerbated by drought stress. Drought stress-responding compounds such as reactive oxygen species (ROS) are associated with fungal stress responsive signaling and secondary metabolite production, and can stimulate the production of aflatoxin by A. flavus in vitro. These secondary metabolites have been shown to possess diverse functions in soil-borne fungi including antibiosis, competitive inhibition of other microbes, and abiotic stress alleviation. Previously, we observed that isolates of A. flavus showed differences in oxidative stress tolerance which correlated with their aflatoxin production capabilities. In order to better understand these isolate-specific oxidative stress responses, we examined the transcriptional responses of field isolates of A. flavus with varying levels of aflatoxin production (NRRL3357, AF13, and Tox4) to H2O2-induced oxidative stress using an RNA sequencing approach. These isolates were cultured in an aflatoxin-production conducive medium amended with various levels of H2O2. Whole transcriptomes were sequenced using an Illumina HiSeq platform with an average of 40.43 million filtered paired-end reads generated for each sample. The obtained transcriptomes were then used for differential expression, gene ontology, pathway, and co-expression analyses. Isolates which produced higher levels of aflatoxin tended to exhibit fewer differentially expressed genes than isolates with lower levels of production. Genes found to be differentially expressed in response to increasing oxidative stress included antioxidant enzymes, primary metabolism components, antibiosis-related genes, and secondary metabolite biosynthetic components specifically for aflatoxin, aflatrem, and kojic acid. The expression of fungal development-related genes including aminobenzoate degradation genes and conidiation regulators were found to be regulated in response to increasing stress. Aflatoxin biosynthetic genes and antioxidant enzyme genes were also found to be co-expressed and highly correlated with fungal biomass under stress. This suggests that these secondary metabolites may be produced as part of coordinated oxidative stress responses in A. flavus along with antioxidant enzyme gene expression and developmental regulation.

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“…The fact that chiB expression is altered in the veA deletion mutant also suggests possible alterations in cell wall composition in this A. flavus strain. This, together with the observed alterations in the expression of tpsA, encoding a phosphate synthase important in trehalose biosynthesis (68), could in part contribute the greater sensitivity to environmental stresses, such as oxidative stress, in the ⌬veA strain (69).…”

Section: Figmentioning

confidence: 99%

Transcriptome Analysis of Aspergillus flavus Reveals veA -Dependent Regulation of Secondary Metabolite Gene Clusters, Including the Novel Aflavarin Cluster

et al. 2015

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eThe global regulatory veA gene governs development and secondary metabolism in numerous fungal species, including Aspergillus flavus. This is especially relevant since A. flavus infects crops of agricultural importance worldwide, contaminating them with potent mycotoxins. The most well-known are aflatoxins, which are cytotoxic and carcinogenic polyketide compounds. The production of aflatoxins and the expression of genes implicated in the production of these mycotoxins are veA dependent. The genes responsible for the synthesis of aflatoxins are clustered, a signature common for genes involved in fungal secondary metabolism. Studies of the A. flavus genome revealed many gene clusters possibly connected to the synthesis of secondary metabolites. Many of these metabolites are still unknown, or the association between a known metabolite and a particular gene cluster has not yet been established. In the present transcriptome study, we show that veA is necessary for the expression of a large number of genes. Twenty-eight out of the predicted 56 secondary metabolite gene clusters include at least one gene that is differentially expressed depending on presence or absence of veA. One of the clusters under the influence of veA is cluster 39. The absence of veA results in a downregulation of the five genes found within this cluster. Interestingly, our results indicate that the cluster is expressed mainly in sclerotia. Chemical analysis of sclerotial extracts revealed that cluster 39 is responsible for the production of aflavarin.A spergillus flavus is a saprophytic filamentous fungus that is also able to colonize economically important crops such as peanuts, cotton, maize, and other oil seed crops during preharvest or storage. Its most efficient mode of dissemination is the production of airborne conidia. In addition, A. flavus produces resistant structures called sclerotia, which allow this fungus to survive adverse environmental conditions for long periods of time (1-3). This opportunistic pathogen produces a wide range of secondary metabolites, including aflatoxins (AFs). Among them, AFB1 is the most mutagenic and carcinogenic natural compound known (4-8). Ingestion of food products contaminated with AFs has been associated with hepatotoxicity, teratogenicity, immunosuppression, and liver cancer (6, 9). AF contamination also results in a negative impact on the economy in developed countries. In the United States alone A. flavus causes more than a billion dollar in losses per year due to contaminated crops (10). In addition to AFs, A. flavus is known to produce other mycotoxins, including cyclopiazonic acid (CPA), a suppressor of the calcium-dependent ATPase in the sarcoplasmic reticulum, and aflatrem, a tremogenic mycotoxin causative of neurological disorders (11,12).Studies of the A. flavus genome have revealed many gene clusters possibly connected to the synthesis of other secondary metabolites. Specifically, 55 different clusters were predicted based on the presence of genes encoding polyketide synthases (PKSs), non...

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VeA Is Associated with the Response to Oxidative Stress in the Aflatoxin Producer Aspergillus flavus

Cited by 64 publications

References 48 publications

Piperine inhibits aflatoxin B1 production in Aspergillus flavus by modulating fungal oxidative stress response

Piperine inhibits aflatoxin B1 production in Aspergillus flavus by modulating fungal oxidative stress response

Responses of Aspergillus flavus to Oxidative Stress Are Related to Fungal Development Regulator, Antioxidant Enzyme, and Secondary Metabolite Biosynthetic Gene Expression

Transcriptome Analysis of Aspergillus flavus Reveals veA -Dependent Regulation of Secondary Metabolite Gene Clusters, Including the Novel Aflavarin Cluster

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