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Schroeckh, V.

Publications and source records attributed to Schroeckh, V..

3 recordsLinked to original sources

The fungal transcription factor SmpR coordinates secondary metabolism and antibacterial defence in Aspergillus fumigatus during interspecies interaction

Aspergillus fumigatus, an opportunistic human fungal pathogen, encodes numerous secondary metabolite biosynthetic gene clusters (BGCs) that are tightly regulated and often remain silent under standard conditions. Co-cultivation with Streptomyces rapamycinicus or treatment with the secondary metabolite from this species, the arginoketide azalomycin F, induce the otherwise silent fumicycline (fcc) BGC of A. fumigatus. To elucidate the underlying regulatory circuitry, we performed transcriptome analyses of A. fumigatus exposed to azalomycin F or co-cultured with S. rapamycinicus. Both conditions triggered a coordinated antibacterial response, characterized by induction of specific secondary metabolites and antibacterial effectors, alongside repression of other BGCs, including those for fusarinine C, pyripyropene A, and fumagillin. Among the most strongly induced genes was a zinc cluster transcription factor, designated SmpR for secondary metabolite multiple pathway regulator, which is conserved within Ascomycota. SmpR expression was selectively induced by azalomycin F, specific Streptomyces species and other bacteria isolated from soil such as Kribbella spp. and Arthrobacter spp.. Functional analyses revealed that SmpR is required for activation of the fumicycline BGC: its deletion reduced, whereas its overexpression enhanced fumicycline production independently of external stimuli. We further demonstrate that SmpR acts upstream of the pathway-specific regulator FccR and additionally controls multiple antibacterial BGCs, including those for hexadehydroastechrome, helvolic acid and xanthocillin. Together, our data identify SmpR as a key regulator coordinating antibacterial secondary metabolism in response to bacterial signals in A. fumigatus.

microbiology↗

Ubiquitous bacterial polyketides induce cross-kingdom microbial interactions

Although the interaction of prokaryotic and eukaryotic microorganisms is critical for the functioning of ecosystems, knowledge of the processes driving microbial interactions within communities is in its infancy. We previously reported that the soil bacterium Streptomyces iranensis specifically triggers the production of natural products in the fungus Aspergillus nidulans. Here, we discovered that arginine-derived polyketides serve as the bacterial signals for this induction. Arginine-derived polyketide-producing bacteria occur world wide. These producer bacteria and the fungi that decode and respond to this signal can be co-isolated from the same soil sample. Arginine-derived polyketides impact surrounding microorganisms both directly as well as indirectly, by inducing the production of natural products in fungi that further influence the composition of microbial consortia. One-Sentence SummaryUbiquitous bacterial polyketides are universal components of the chemical network for microbial communication

microbiology↗

Bacterium-triggered remodeling of chromatin identifies BasR, a novel regulator of fungal natural product biosynthesis

The eukaryotic epigenetic machinery is targeted by bacteria to reprogram the response of eukaryotes during their interaction with microorganisms. In line, we discovered that the bacterium Streptomyces rapamycinicus triggered increased chromatin acetylation and thus activation of the silent secondary metabolism ors gene cluster leading to the production of orsellinic acid in the fungus Aspergillus nidulans. Using this model we aim at understanding molecular mechanisms of communication between bacteria and eukaryotic microorganisms based on bacteria-triggered chromatin modification. By genome-wide ChIP-seq analysis of acetylated histone H3 (H3K9ac, H3K14ac) we uncovered the unique chromatin landscape in A. nidulans upon co-cultivation with S. rapamycinicus. Genome-wide acetylation of H3K9 correlated with increased gene expression, whereas H3K14 appears to function in transcriptional initiation by providing a docking side for regulatory proteins. In total, histones belonging to six secondary metabolism gene clusters showed higher acetylation during co-cultivation including the ors, aspercryptin, cichorine, sterigmatocystin, anthrone and 2,4-dihydroxy-3-methyl-6-(2-oxopropyl)benzaldehyde gene cluster with the emericellamide cluster being the only one with reduced acetylation and expression. Differentially acetylated histones were also detected in genes involved in amino acid and nitrogen metabolism, signaling, and genes encoding transcription factors. In conjunction with LC-MS/MS and MALDI-MS imaging, molecular analyses revealed the cross-pathway control and Myb-like transcription factor BasR as regulatory nodes for transduction of the bacterial signal in the fungus. The presence of basR in other fungal species allowed forecasting the inducibility of ors-like gene clusters by S. rapamycinicus in these fungi, and thus their effective interaction with activation of otherwise silent gene clusters.

microbiology↗