Polaramycin B, and not physical interaction, is the signal that rewires fungal metabolism in the Streptomyces-Aspergillus interaction.

Co-culturing the bacterium Streptomyces rapamycinicus and the ascomycete Aspergillus nidulans has previously been shown to trigger the production of orsellinic acid (ORS) and its derivates in the fungal cells. Based on these studies it was assumed that direct physical contact is a prerequisite for the metabolic reaction that involves a fungal amino acid starvation response and activating chromatin modifications at the biosynthetic gene cluster (BGC). Here we show that not physical contact, but a guanidine containing macrolide, named polaramycin B, triggers the response. The substance is produced constitutively by the bacterium and above a certain concentration, provokes the production of ORS. In addition, several other secondary metabolites were induced by polaramycin B. Our genome-wide transcriptome analysis showed that polaramycin B treatment causes downregulation of fungal genes necessary for membrane stability, general metabolism and growth. A compensatory genetic response can be observed in the fungus that included upregulation of BGCs and genes necessary for ribosome biogenesis, translation and membrane stability. Our work discovered a novel chemical communication, in which the antifungal bacterial metabolite polaramycin B leads to the production of antibacterial defence chemicals and to the upregulation of genes necessary to compensate for the cellular damage caused by polaramycin B.

RimO (SrrB) is required for carbon starvation signaling and production of secondary metabolites in Aspergillus nidulans.

Depending on the prevailing environmental, developmental and nutritional conditions, fungi activate biosynthetic gene clusters (BGCs) to produce condition-specific secondary metabolites (SMs). For activation, global chromatin-based de-repression must be integrated with pathway-specific induction signals. Here we describe a new global regulator needed to activate starvation-induced SMs. In our transcriptome dataset, we found locus AN7572 strongly transcribed solely under conditions of starvation-induced SM production. The predicted AN7572 protein is most similar to the stress and nutritional regulator Rim15 of Saccharomyces cerevisiae, and to STK-12 of Neurospora crassa. Based on this similarity and on stress and nutritional response phenotypes of A. nidulans knock-out and overexpression strains, AN7572 is designated rimO. In relation to SM production, we found that RimO is required for the activation of starvation-induced BGCs, including the sterigmatocystin (ST) gene cluster. Here, RimO regulates the pathway-specific transcription factor AflR both at the transcriptional and post-translational level. At the transcriptional level, RimO mediates aflR induction following carbon starvation and at the post-translational level, RimO is required for nuclear accumulation of the AflR protein. Genome-wide transcriptional profiling showed that cells lacking rimO fail to adapt to carbon starvation that, in the wild type, leads to down-regulation of genes involved in basic metabolism, membrane biogenesis and growth. Consistently, strains overexpressing rimO are more resistant to oxidative and osmotic stress, largely insensitive to glucose repression and strongly overproduce several SMs. Our data indicate that RimO is a positive regulator within the SM and stress response network, but this requires nutrient depletion that triggers both, rimO gene transcription and activation of the RimO protein.

Naturally Occurring Phenols Modulate Vegetative Growth and Deoxynivalenol Biosynthesis in Fusarium graminearum.

To assess the in vitro activity of five naturally occurring phenolic compounds (ferulic acid, apocynin, magnolol, honokiol, and thymol) on mycelial growth and type B trichothecene mycotoxin accumulation by Fusarium graminearum, three complementary approaches were adopted. First, a high-throughput photometric continuous reading array allowed a parallel quantification of F. graminearum hyphal growth and reporter TRI5 gene expression directly on solid medium. Second, RT-qPCR confirmed the regulation of TRI5 expression by the tested compounds. Third, liquid chromatography-tandem mass spectrometry analysis allowed quantification of deoxynivalenol (DON) and its acetylated forms released upon treatment with the phenolic compounds. Altogether, the results confirmed the activity of thymol and an equimolar mixture of thymol-magnolol at 0.5 mM, respectively, in inhibiting DON production without affecting vegetative growth. The medium pH buffering capacity after 72-96 h of incubation is proposed as a further element to highlight compounds displaying trichothecene inhibitory capacity with no significant fungicidal effect.