Distinct Roles for VeA and LaeA in Development and Pathogenesis ofAspergillus flavus

Abstract

Aspergillus flavus, a mycotoxigenic filamentous fungus, colonizes several important agricultural crops, such as maize and peanuts. Two proteins, VeA and LaeA, known to form a nuclear complex in Aspergillus nidulans have been found to positively regulate developmental processes in several Aspergillus species. Here, an examination of near-isogenic A. flavus mutants differing in copy number of veA and laeA alleles (0, 1, or at least 2 each) revealed critical roles for VeA and LaeA in A. flavus development and seed colonization. In contrast to the wild type, both null mutants were unable to metabolize host cell lipid reserves and were inhibited by oleic acid in growth assays. The copy number of LaeA but not VeA appeared critical for a density-dependent sclerotial-to-conidial shift, since the multicopy laeA (MClaeA) strain produced relatively constant sclerotial numbers with increasing population size rather than showing the decrease in sclerotia seen in both the wild-type and MCveA strains. The MCveA-laeA strain yielded an intermediate phenotype. This study revealed unique roles of VeA and LaeA in seed pathogenesis and fungal biology, distinct from their cooperative regulatory functions in aflatoxin and sclerotial development.

Suppressor Mutagenesis Identifies a Velvet Complex Remediator of Aspergillus nidulans Secondary Metabolism

“…Two critical members of the Velvet complex are LaeA, a global regulator of SM (1,5,8,29), and VeA, or velvet, involved in the regulation of diverse cellular processes, including asexual and sexual development (11,28) as well as secondary metabolism (26,31). Deletion of either gene leads to a loss or decrease of SM production, and overexpression leads to enhanced production (1,5,8,20,26,43). Currently, the manner in which Velvet controls SM production is unknown, although LaeA activity is increasingly linked to chromatin modifications (37,40).…”

“…LaeA, a putative methyltransferase, was first identified in Aspergillus nidulans (5), A. fumigatus (6), and, subsequently, A. flavus (25). Overexpression (OE) of laeA increases the production of multiple metabolites in the aspergilli, whereas deletion of laeA silences expression of SM genes (1,5,8,20). LaeA is thus used as a genomic mining tool, providing a novel method for identifying new SM through microarray and chemical analyses (8,20,34).…”

“…LaeA is thus used as a genomic mining tool, providing a novel method for identifying new SM through microarray and chemical analyses (8,20,34). Moreover, deletion of laeA in A. fumigatus decreases the virulence of this human pathogen (4,6); similarly, A. flavus laeA deletants are also reduced in virulence on host seed (1,25). LaeA homologs are also found in other filamentous fungi such as Penicillium chrysogenum and Fusarium fujikuroi, where they control SM, pigmentation, sporulation, and virulence (29,43).…”

Reproduction without sex: conidiation in the filamentous fungus Trichoderma

“…In N. crassa, A. nidulans and Penicillium chrysogenum, deletion of veA orthologues leads to an increase in light-independent conidial formation, whereas deletion in Aspergillus parasiticus and Aspergillus fumigatus results in a general decrease in conidiation, which is dependent on the nutritional composition of the medium (Bayram et al, 2008;Calvo et al, 2004;Hoff et al, 2010, Krappmann et al, 2005Mooney & Yager, 1990). A reduction in conidiation has also been observed in Aspergillus flavus and Fusarium fujikuroi veA orthologue deletion mutants (Amaike & Keller, 2009;Wiemann et al, 2010).…”

Conserved Regulatory Mechanisms Controlling Aflatoxin and Sterigmatocystin Biosynthesis

“…In A. flavus it has been shown that laeA is a negative regulator of veA transcription (Kale et al, 2008). In addition, increased expression of veA (in a strain with multiple veA copies) results in decreased laeA expression (Amaike and Keller, 2009), suggesting a mutual negative transcriptional regulatory feedback control. In addition to transcriptional regulation between veA and laeA, recent studies also suggest posttranslational regulation (Bayram et al, 2010); a new form of the VeA protein with higher molecular weight has been detected in laeA strains, indicating that in the wild type, laeA prevents a modification of the VeA protein (Bayram et al, 2010).…”