An Aspergillus nidulans bZIP response pathway hardwired for defensive secondary metabolism operates through aflR

Abstract

Summary The eukaryotic bZIP transcription factors are critical players in organismal response to environmental challenges. In fungi, the production of secondary metabolites (SMs) is hypothesized as one of the responses to environmental insults, e.g. attack by fungivorous insects, yet little data to support this hypothesis exists. Here we establish a mechanism of bZIP regulation of SMs through RsmA, a recently discovered YAP-like bZIP protein. RsmA greatly increases SM production by binding to two sites in the A. nidulans AflR promoter region, a C6 transcription factor known for activating production of the carcinogenic and anti-predation SM, sterigmatocystin (ST). Deletion of aflR in an overexpression rsmA (OE::rsmA) background not only eliminates ST production but also significantly reduces asperthecin synthesis. Furthermore, the fungivore, Folsomia candida, exhibited a distinct preference for feeding on wild type rather than an OE::rsmA strain. RsmA may thus have a critical function in mediating direct chemical resistance against predation. Taken together, these results suggest RsmA represents a bZIP pathway hardwired for defensive SM production.

Aspergillus parasiticus SU-1 Genome Sequence, Predicted Chromosome Structure, and Comparative Gene Expression under Aflatoxin-Inducing Conditions: Evidence that Differential Expression Contributes to Species Phenotype

“…Members of the C6 transcription factor family are particularly interesting, because they are specific to fungi and are strongly associated with many secondary metabolism gene clusters in both (18). These observations suggest that the C6 transcription factors play an important role in regulating secondary metabolism and that we could target them to modulate secondary metabolite expression without affecting the host plant or humans that consume crops associated with mycotoxins.…”

Fungal metabolic plasticity and sexual development mediate induced resistance to arthropod fungivory

“…By contrast, chemical deficient A. nidulans colonies were exploited unevenly [15], which prompted us to hypothesize that the induced change in resistance to fungivores is linked to dynamics in secondary metabolite biosynthesis, in particular ST [16]. To test this we directly quantified ST by HPLC-MS/MS and electronic supplementary material, figure S5).…”

“…Body lengths were averaged for each arena to obtain one measurement per arena. Additionally, we counted the number faecal pellets to provide a measure of feeding intensity [16]. The same setup was used for quantifying cleistothecia on A. nidulans colonies that were exposed to groups of three F. candida for 6 days.…”

“…Autoclaved glass fibre filters discs (1.0 cm in diameter, MN85/70 BF, Macherey-Nagel GmbH & Co. KG, Germany) were soaked in melted malt extract agar [16]. After hardening, each disc was inoculated with 2 ml of a conidial suspension (1000 conidia per ml).…”

“…For time-dependent food choice we applied mixed repeated measurement models as described previously [15,16]. Depending on data properties parametric one-way ANOVA (measure of metabolite formation, fungivore body size, faecal pellets), onesample t-tests ( post hoc analysis of fungivore food choice) or non-parametric tests (cleistothecia count) were used.…”