ABSTRACT
The eukaryotic epigenetic machinery can be modified by bacteria to reprogram the response of eukaryotes during their interaction with microorganisms. We discovered that the bacterium Streptomyces rapamycinicus triggered increased chromatin acetylation and thus activation of the silent secondary metabolism ors gene cluster in the fungus Aspergillus nidulans. Using this model, we aim understanding mechanisms of microbial communication based on bacteria-triggered chromatin modification. Using genome-wide ChIP-seq analysis of acetylated histone H3, we uncovered the unique chromatin landscape in A. nidulans upon co-cultivation with S. rapamycinicus and relate changes in the acetylation to that in the fungal transcriptome. Differentially acetylated histones were detected in genes involved in secondary metabolism, in amino acid and nitrogen metabolism, in signaling, and encoding transcription factors. Further molecular analyses identified the Myb-like transcription factor BasR as the regulatory node for transduction of the bacterial signal in the fungus and show its function is conserved in other Aspergillus species.
Subject(s)
Aspergillus nidulans/metabolism , Chromatin/metabolism , Fungal Proteins/metabolism , Secondary Metabolism , Streptomyces/metabolism , Acetylation , Aspergillus nidulans/genetics , Fungal Proteins/genetics , Gene Expression Regulation, Fungal , Gene Ontology , Genome, Fungal , Histidine/metabolism , Histones/metabolism , Lysine/metabolism , Mitochondria/metabolism , Multigene Family , Nitrogen/metabolism , Phylogeny , Signal Transduction , Transcription Factors/metabolismABSTRACT
Since the discovery of penicillin, antibiotics have been instrumental in treating infectious diseases. However, emerging antibiotic multi-resistance coinciding with a nearly exhausted drug pipeline is a major concern for the future of the therapy of infections. A novel approach for the discovery of antibiotics relies on the analysis of microbial consortia in their ecological context, taking into account the potential natural role of antibiotics. Co-cultivations of microorganisms have been successfully applied for the isolation of unknown secondary metabolites including antibiotics, and, thus, open new avenues to the production of bioactive compounds while at the same time providing insight into the natural function of the produced molecules and the regulation of their formation.
