The bZIP Protein MeaB Mediates Virulence Attributes in Aspergillus flavus

Abstract

LaeA is a fungal specific virulence factor of both plant and human pathogenic fungi. Transcriptional profiles of laeA mutants have been successfully exploited to identify regulatory mechanisms of secondary metabolism in fungi; here we use laeA mutants as tools to elucidate virulence attributes in Aspergillus flavus. Microarray expression profiles of ΔlaeA and over-expression laeA (OE::laeA) were compared to wild type A. flavus. Strikingly, several nitrogen metabolism genes are oppositely mis-regulated in the ΔlaeA and OE::laeA mutants. One of the nitrogen regulatory genes, the bZIP encoding meaB, is up-regulated in ΔlaeA. Significantly, over-expression of meaB (OE::meaB) phenocopies the decreased virulence attributes of a ΔlaeA phenotype including decreased colonization of host seed, reduced lipase activity and loss of aflatoxin B1 production in seed. However, a double knock-down of laeA and meaB (KD::laeA,meaB) demonstrated that KD::laeA,meaB closely resembled ΔlaeA rather than wild type or ΔmeaB in growth, aflatoxin biosynthesis and sclerotia production thus suggesting that meaB does not contribute to the ΔlaeA phenotype. MeaB and LaeA appear to be part of regulatory networks that allow them to have both shared and distinct roles in fungal biology.

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

“…The protein NmrA was defined as a repressor of the GATA transcription factor AreA, which regulates several genes required for utilization of less preferred nitrogen sources (Caddick et al, 1986; Andrianopoulos et al, 1998; Tudzynski, 2014), and the bZIP protein MeaB was proposed to activate NmrA in A. nidulans (Wong et al, 2007; López-Berges et al, 2010; Amaike et al, 2013). AreA, MeaB, and NmrA and are conserved in filamentous fungi (Wagner et al, 2010).…”

“…However, recent studies showed that nmrA expression in A. nidulans and F. fujikuroi is not MeaB-dependent (Wagner et al, 2010; Amaike et al, 2013), and MeaB and AreA mediate nitrogen repression coordinately while also functioning independently (Wong et al, 2007; Wagner et al, 2010). Moreover, the ability of AreA and AreB to respond to carbon status probably depends on NmrA rather than the transcription factor CreA, which mediates CCR in A. nidulans (Macios et al, 2012).…”

“…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. AF contamination of agricultural grains is not only a significant food safety concern but also an economic concern for the agricultural industry worldwide (Yu, 2012; Amaike et al, 2013; Yang et al, 2015). To develop effective and novel strategies against AF contamination, it is a necessity to investigate the molecular mechanisms by which AF biosynthesis is regulated in A. flavus .…”

Key Players in the Regulation of Fungal Secondary Metabolism

“…bZIPs associated with SM regulation and stress include RsmA regulating sterigmatocystin and asperthecin in A. nidulans and gliotoxin in A. fumigatus [64,65], AtfB regulating aflatoxin in Aspergillus parasiticus [60], and Aoyap1 regulating ochratoxin in Aspergillus ochraceus [59]. The bZIP protein MeaB, involved in nitrogen regulation, has also been associated with regulation of SMs including bikaverin in F. fujikuroi and AF in A. flavus [62,63].…”

The bZIP Transcription Factor AflRsmA Regulates Aflatoxin B1 Biosynthesis, Oxidative Stress Response and Sclerotium Formation in Aspergillus flavus

“…Among the regulators, several bZIP transcription factors mediate virulence and secondary metabolism [29]. In A. flavus, bZIP TF MeaB regulates secondary metabolism and virulence [30]. AtfB regulates aflatoxin production by binding to the promoters of seven aflatoxin biosynthesis genes that carry CREs [10].…”