Dataset Information

The epigenetic reader SntB regulates secondary metabolism, development and global histone modifications in Aspergillus flavus.

ABSTRACT: Due to the role, both beneficial and harmful, that fungal secondary metabolites play in society, the study of their regulation is of great importance. Genes for any one secondary metabolite are contiguously arranged in a biosynthetic gene cluster (BGC) and subject to regulation through the remodeling of chromatin. Histone modifying enzymes can place or remove post translational modifications (PTM) on histone tails which influences how tight or relaxed the chromatin is, impacting transcription of BGCs. In a recent forward genetic screen, the epigenetic reader SntB was identified as a transcriptional regulator of the sterigmatocystin BGC in A. nidulans, and regulated the related metabolite aflatoxin in A. flavus. In this study we investigate the role of SntB in the plant pathogen A. flavus by analyzing both ?sntB and overexpression sntB genetic mutants. Deletion of sntB increased global levels of H3K9K14 acetylation and impaired several developmental processes including sclerotia formation, heterokaryon compatibility, secondary metabolite synthesis, and ability to colonize host seeds; in contrast the overexpression strain displayed fewer phenotypes. ?sntB developmental phenotypes were linked with SntB regulation of NosA, a transcription factor regulating the A. flavus cell fusion cascade.

SUBMITTER: Pfannenstiel BT

PROVIDER: S-EPMC6215504 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature

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The epigenetic reader SntB regulates secondary metabolism, development and global histone modifications in Aspergillus flavus.

Pfannenstiel Brandon T BT Greco Claudio C Sukowaty Andrew T AT Keller Nancy P NP

Fungal genetics and biology : FG & B 20180818

Due to the role, both beneficial and harmful, that fungal secondary metabolites play in society, the study of their regulation is of great importance. Genes for any one secondary metabolite are contiguously arranged in a biosynthetic gene cluster (BGC) and subject to regulation through the remodeling of chromatin. Histone modifying enzymes can place or remove post translational modifications (PTM) on histone tails which influences how tight or relaxed the chromatin is, impacting transcription of ...[more]

PMID: 30130575

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Project description:Aspergillus flavus is an opportunistic fungal plant and human pathogen and a producer of mycotoxins, including aflatoxin B1 (AFB1). As part of our ongoing studies to elucidate the biological functions of the A. flavusrtfA gene, we examined its role in the pathogenicity of both plant and animal model systems. rtfA encodes a putative RNA polymerase II (Pol II) transcription elongation factor previously characterized in Saccharomyces cerevisiae, Aspergillus nidulans, and Aspergillus fumigatus, where it was shown to regulate several important cellular processes, including morphogenesis and secondary metabolism. In addition, an initial study in A. flavus indicated that rtfA also influences development and production of AFB1; however, its effect on virulence is unknown. The current study reveals that the rtfA gene is indispensable for normal pathogenicity in plants when using peanut seed as an infection model, as well as in animals, as shown in the Galleria mellonella infection model. Interestingly, rtfA positively regulates several processes known to be necessary for successful fungal invasion and colonization of host tissue, such as adhesion to surfaces, protease and lipase activity, cell wall composition and integrity, and tolerance to oxidative stress. In addition, metabolomic analysis revealed that A. flavusrtfA affects the production of several secondary metabolites, including AFB1, aflatrem, leporins, aspirochlorine, ditryptophenaline, and aflavinines, supporting a role of rtfA as a global regulator of secondary metabolism. Heterologous complementation of an A. flavusrtfA deletion strain with rtfA homologs from A. nidulans or S. cerevisiae fully rescued the wild-type phenotype, indicating that these rtfA homologs are functionally conserved among these three species.IMPORTANCE In this study, the epigenetic global regulator rtfA, which encodes a putative RNA-Pol II transcription elongation factor-like protein, was characterized in the mycotoxigenic and opportunistic pathogen A. flavus Specifically, its involvement in A. flavus pathogenesis in plant and animal models was studied. Here, we show that rtfA positively regulates A. flavus virulence in both models. Furthermore, rtfA-dependent effects on factors necessary for successful invasion and colonization of host tissue by A. flavus were also assessed. Our study indicates that rtfA plays a role in A. flavus adherence to surfaces, hydrolytic activity, normal cell wall formation, and response to oxidative stress. This study also revealed a profound effect of rtfA on the metabolome of A. flavus, including the production of potent mycotoxins.

Project description:The opportunistic plant-pathogenic fungus Aspergillus flavus produces carcinogenic mycotoxins termed aflatoxins (AF). Aflatoxin contamination of agriculturally important crops, such as maize, peanut, sorghum, and tree nuts, is responsible for serious adverse health and economic impacts worldwide. In order to identify possible genetic targets to reduce AF contamination, we have characterized the artA gene, encoding a putative 14-3-3 homolog in A. flavus The artA deletion mutant presents a slight decrease in vegetative growth and alterations in morphological development and secondary metabolism. Specifically, artA affects conidiation, and this effect is influenced by the type of substrate and culture condition. In addition, normal levels of artA are required for sclerotial development. Importantly, artA negatively regulates AF production as well as the concomitant expression of genes in the AF gene cluster. An increase in AF is also observed in seeds infected with the A. flavus strain lacking artA Furthermore, the expression of other secondary metabolite genes is also artA dependent, including genes in the cyclopiazonic acid (CPA) and ustiloxin gene clusters, in this agriculturally important fungus.IMPORTANCE In the current study, artA, which encodes a 14-3-3 homolog, was characterized in the agriculturally and medically important fungus Aspergillus flavus, specifically, its possible role governing sporulation, formation of resistant structures, and secondary metabolism. The highly conserved artA is necessary for normal fungal morphogenesis in an environment-dependent manner, affecting the balance between production of conidiophores and the formation of resistant structures that are necessary for the dissemination and survival of this opportunistic pathogen. This study reports a 14-3-3 protein affecting secondary metabolism in filamentous fungi. Importantly, artA regulates the biosynthesis of the potent carcinogenic compound aflatoxin B1 (AFB1) as well as the production of other secondary metabolites.

Dataset Information

The epigenetic reader SntB regulates secondary metabolism, development and global histone modifications in Aspergillus flavus.

Publications

The epigenetic reader SntB regulates secondary metabolism, development and global histone modifications in Aspergillus flavus.

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