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Requirement of LaeA for secondary metabolism and sclerotial production in Aspergillus flavus.

ABSTRACT: The nuclear regulator LaeA has been shown to govern production of multiple secondary metabolites in Aspergillus nidulans and Aspergillus fumigatus. Herein we examine the role of this protein in Aspergillus flavus. Similarly as in other Aspergilli, LaeA had a major effect on A. flavus secondary metabolism where DeltalaeA and over-expression laeA (OE::laeA) strains yielded opposite phenotypes resulting in decreased (increased) secondary metabolite production. The two mutant strains also exhibited striking morphological phenotypes in the loss (increase) of sclerotial production in comparison to wildtype. Growth on seed was marked by decreased (increased) conidial and aflatoxin production of the respective mutants; this was accompanied by decreased lipase activity in DeltalaeA, an enzymatic process correlated with seed maceration. Transcriptional examination of the mutants showed LaeA negatively regulates expression of its recently identified nuclear partner VeA, another global regulator of A. flavus secondary metabolites and sclerotia.

SUBMITTER: Kale SP

PROVIDER: S-EPMC2845523 | biostudies-literature | 2008 Oct

REPOSITORIES: biostudies-literature

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Requirement of LaeA for secondary metabolism and sclerotial production in Aspergillus flavus.

Kale Shubha P SP Milde Lane L Trapp Marisa K MK Frisvad Jens C JC Keller Nancy P NP Bok Jin Woo JW

Fungal genetics and biology : FG & B 20080711 10

The nuclear regulator LaeA has been shown to govern production of multiple secondary metabolites in Aspergillus nidulans and Aspergillus fumigatus. Herein we examine the role of this protein in Aspergillus flavus. Similarly as in other Aspergilli, LaeA had a major effect on A. flavus secondary metabolism where DeltalaeA and over-expression laeA (OE::laeA) strains yielded opposite phenotypes resulting in decreased (increased) secondary metabolite production. The two mutant strains also exhibited ...[more]

PMID: 18667168

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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.

Dataset Information

Requirement of LaeA for secondary metabolism and sclerotial production in Aspergillus flavus.

Publications

Requirement of LaeA for secondary metabolism and sclerotial production in Aspergillus flavus.

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