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Project B02

Principal Investigators: Prof. Dr. A. Brakhage, Prof. Dr. T. Heinzel

Mechanisms of Bacteria-triggered Activation of Fungal Silent Gene Clusters and Impact of Produced Compounds on Microorganisms


Elucidation of the specific interaction between microorganisms is one of the emerging fields in microbiology and chemical biology. Recently, we discovered that the important model fungus Aspergillus nidulans specifically interacts with a distinct bacterium, i.e., Streptomyces rapamycinicus. As a consequence, the silent ors gene cluster is activated in the fungus, which leads to the formation of orsellinic acid, lecanoric acid and derivatives thereof. Continuation of this work by us led to the discovery that the bacterium is able to trigger alterations of histone acetylation in the fungus, which are specifically associated with the activated gene cluster. For this activation process, S. rapamycinicus re-programs the histone acetyltransferase GcnE-containing Saga/Ada complex of A. nidulans. Consequently, the histone H3 amino acids K9 and K14 at distinct secondary metabolism genes were specifically acetylated during the bacterial fungal interaction, whereas the K14 acetylation was of major importance. Furthermore, we know that also environmental factors influence the activation of the ors gene cluster and, most likely, that the produced compounds affect the structure of microbial communities.

Model of complex interactions between S. rapamycinicus and A. nidulans.

The specific interaction between A. nidulans and S. rapamycinicus now provides an excellent model system to elucidate the underlying molecular mechanisms leading to the activation of a silent secondary metabolism gene cluster by a bacterium. Based on these previous findings, in this proposal, we will (i) identify the entirely unknown signals deriving from the bacterium by applying a transposon knock-out library and, moreover, the corresponding fungal receptors like components of the Saga/Ada complex leading to the activation of the ors gene cluster, (ii) identify the downstream targets of the chromatin-modifying Saga/Ada complex in response to the bacterium by RNA sequencing and proteome analyses of the histone acetyltransferase gcnE mutant, (iii) identify counteracting HDACs and their complexes and (iv) elucidate how chromatin-modifying complexes are targeted to certain regions of the chromosome in response to specific bacterial signals. This will be achieved by analyzing the protein complexes on the ors promoters under standard (non-inducing) and inducing conditions during co-cultivation of bacterium and fungus by chromatin immune precipitation of proteins cross-linked to the DNA of the promoters of ors genes. (v) Finally, we will identify the impact of orsellinic acid and its derivatives on structuring microbial communities or, at least, on other microorganisms. These studies will provide fundamental insights into epigenetic regulation of secondary metabolites in response to microbial communication and will potentially allow insights into entirely novel mechanisms of epigenetic control of gene clusters.

Team B02

Prof Dr. Axel Brakhage


Institute of Microbiology, Friedrich Schiller University Jena and Department for Molecular and Applied Microbiology

Leibniz Institute for Natural Product Research and Infection Biology – Hans-Knöll-Institute

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Prof Dr. Thorsten Heinzel


Department of Biochemistry, Center for Molecular Biomedicine

Friedrich Schiller University Jena

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Dr. Tina Netzker


Department for Molecular and Applied Microbiology

Leibniz Institute for Natural Product Research and Infection Biology – Hans-Knöll-Institute

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Nils Jäger


Department of Biochemistry, Center for Molecular Biomedicine

Friedrich Schiller University Jena

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Mario Krespach


Department for Molecular and Applied Microbiology

Leibniz Institute for Natural Product Research and Infection Biology – Hans-Knöll-Institute

 

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