Integrative analyses reveal transcriptome-proteome correlation in biological pathways and secondary metabolism clusters in A. flavus in response to temperature

Bai, Youhuang; Wang, Sen; Zhong, Hong; Yang, Qi; Zhang, Na; Zhang, Zhuang; Yuan, Jun; Nie, Xiaowei; Wang, Shihua

doi:10.1038/srep14582

Cited by 94 publications

(104 citation statements)

References 42 publications

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“…In addition, these differential expression patterns of aflatoxin biosynthetic genes may also be indicative of post-transcriptional regulation of aflatoxin production and oxidative stress responses at either the RNA or protein level. For example, there has been a low degree of correlation observed between gene expression and proteomics data for traits such as temperature stress ( r = 0.14) suggesting post-transcriptional regulation of protein accumulation in A. flavus (Bai et al, 2015). Also, given that aflatoxin biosynthetic gene expression can be detected as early as 8 h in culture, there is ample opportunity for such regulation to have a significant effect on later responses to stress and warrants further investigation (Price et al, 2006).…”

Section: Discussionmentioning

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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Section: Discussionmentioning

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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“…This pathway could be affected by many biotic and abiotic factors, including nutritional factors such as carbon and nitrogen sources and environmental factors such as water activity and temperature (Yu, 2012; Amare and Keller, 2014; Zhang et al, 2014, 2015; Bai et al, 2015a,b). In this study, deletion of nmrA resulted in reduced AF production only in the presence of glutamine or alanine, suggesting that the effect of nmrA on AF biosynthesis is mediated by nitrogen sources and that additional factors must be involved in nitrogen regulation, particularly in the regulation of AF biosynthesis.…”

Section: Discussionmentioning

confidence: 99%

“…Aspergillus flavus is ubiquitous in soil and can infect or contaminate a wide range of organic nutrient sources, such as economically important commodities, insects, animal carcasses, and even immunocompromised humans and animals (Amaike and Keller, 2011; Yu, 2012; Zhang et al, 2014; Bai et al, 2015a,b; Zhang et al, 2015). Aflatoxins (AFs), mainly produced by A. flavus and A. parasiticus , have been identified as a class of the most toxic and carcinogenic secondary metabolites of fungi.…”

Section: Introductionmentioning

confidence: 99%

Functional Analysis of the Nitrogen Metabolite Repression Regulator Gene nmrA in Aspergillus flavus

et al. 2016

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In Aspergillus nidulans, the nitrogen metabolite repression (NMR) regulator NmrA plays a major role in regulating the activity of the GATA transcription factor AreA during nitrogen metabolism. However, the function of nmrA in A. flavus has not been previously studied. Here, we report the identification and functional analysis of nmrA in A. flavus. Our work showed that the amino acid sequences of NmrA are highly conserved among Aspergillus species and that A. flavus NmrA protein contains a canonical Rossmann fold motif. Deletion of nmrA slowed the growth of A. flavus but significantly increased conidiation and sclerotia production. Moreover, seed infection experiments indicated that nmrA is required for the invasive virulence of A. flavus. In addition, the ΔnmrA mutant showed increased sensitivity to rapamycin and methyl methanesulfonate, suggesting that nmrA could be responsive to target of rapamycin signaling and DNA damage. Furthermore, quantitative real-time reverse transcription polymerase chain reaction analysis suggested that nmrA might interact with other nitrogen regulatory and catabolic genes. Our study provides a better understanding of NMR and the nitrogen metabolism network in fungi.

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“…This fungus is also one of the most opportunistic pathogen of human and animals causing aspergillosis diseases or liver cancer either through consumption of contaminated food or through invasive growth (Hedayati et al, 2007; Amaike and Keller, 2011; Yang et al, 2015). Because of this, A. flavus causes food shortages, significant economic losses and health problems all over the world especially in warm and moist fields (Amaike and Keller, 2011; Bai et al, 2015). Effective strategies of combating this pathogen are required to alleviate its potential deleterious effects.…”

Section: Introductionmentioning

confidence: 99%

Adenylate Cyclase AcyA Regulates Development, Aflatoxin Biosynthesis and Fungal Virulence in Aspergillus flavus

Yang

Qin

Liu

et al. 2016

Front. Cell. Infect. Microbiol.

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Aspergillus flavus is one of the most important opportunistic pathogens of crops and animals. The carcinogenic mycotoxin, aflatoxins produced by this pathogen cause a health problem to human and animals. Since cyclic AMP signaling controls a range of physiological processes, like fungal development and infection when responding to extracellular stimuli in fungal pathogens, in this study, we investigated the function of adenylate cyclase, a core component of cAMP signaling, in aflatoxins biosynthesis and virulence on plant seeds in A. flavus. A gene replacement strategy was used to generate the deletion mutant of acyA that encodes the adenylate cyclase. Severe defects in fungal growth, sporulation and sclerotia formation were observed in the acyA deletion mutant. The defect in radical growth could be partially rescued by exogenous cAMP analog. The acyA mutant was also significantly reduced in aflatoxins production and virulence. Similar to the former studies in other fungi, The acyA mutant showed enhancing tolerance to oxidative stress, but more sensitive to heat stress. Overall, the pleiotropic defects of the acyA deletion mutant indicates that the cAMP-PKA pathway is involved in fungal development, aflatoxins biosynthesis and plant seed invasion in A. flavus.

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Integrative analyses reveal transcriptome-proteome correlation in biological pathways and secondary metabolism clusters in A. flavus in response to temperature

Cited by 94 publications

References 42 publications

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

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

Functional Analysis of the Nitrogen Metabolite Repression Regulator Gene nmrA in Aspergillus flavus

Adenylate Cyclase AcyA Regulates Development, Aflatoxin Biosynthesis and Fungal Virulence in Aspergillus flavus

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