The bioactive microbiome - host protection on demand

The overall aim is to unravel the role of microbiota in host protection by producing bioactive compounds in response to host-derived signals, and to harness this knowledge to develop beneficial microbes that can be used for disease prevention. We will analyze the role of host-pathogen interactions and establish the role of host-specific signaling in the control of natural product biosynthesis by actinobacteria, especially, in antibiotic production. From metagenomic data sets (e.g. Human Microbiome Project), we know that thousands of biosynthetic gene clusters (BGCs) are encoded by the human microbiome – most of them yet uncharacterized. Additionally, a huge variety of species is present in the gut microbiome with a significant amount of them never been isolated. It has also been observed, that bacteria, that are culturable with the available methods, do often not express (all) their BGCs under standard laboratory conditions, as they are highly regulated upon ecological signals. The challenge is to identify culturing conditions that elicit the biosynthesis of the bioactive compounds, so that their function and structure can be studied. Host-associated bacteria might produce antibiotic compounds in the presence of host stress signals, which has been shown for plant-associated bacteria. We will use a combination of metabolomics and bioassays to determine changes in the secondary metabolites production upon the addition of human hormones and other potential signalling molecules. The focus lays on secondary metabolites with antimicrobial activity.