Filamentous Actinobacteria, such as Streptomyces, produce a plethora of chemically diverse bioactive metabolites that have found applications across medicine, agriculture and biotechnology. Yet,... Show moreFilamentous Actinobacteria, such as Streptomyces, produce a plethora of chemically diverse bioactive metabolites that have found applications across medicine, agriculture and biotechnology. Yet, the vast majority of the biosynthetic potential of Actinobacteria remains uncharacterised, largely because their biosynthetic gene clusters (BGCs) are poorly expressed in the laboratory, preventing the discovery of the cognate natural products. Additionally, only a narrow band of environments and a few taxonomic groups have been explored for gifted Actinobacteria. In this thesis different approaches are described, wherein we combined drug discovery with ecology, aimed at accessing the full potential of Actinobacteria. Bioactive Actinobacteria were isolated from a faecal sample of a 28,000-year-old-mammoth and their taxonomic and metabolic diversity was analysed. Furthermore, the effect of human stress hormones on the production of antibiotics by Streptomyces was investigated, resulting in the discovery of adrenaline as elicitor of siderophore production. This was later shown to be caused by the adrenaline analog catechol, which is ubiquitous in nature. Catechol also elicited the production of angucycline glycosides, well known for their therapeutic potential as anticancer and antibiotic compounds. Lastly, zebrafish were used as an in vivo model to explore the bioactive and functional potential of Actinobacteria within the animal microbiome. Show less
Plants are colonized by an astounding number of microorganisms that can provide different life-support functions, including nutrient acquisition and protection against (a)biotic stresses like... Show morePlants are colonized by an astounding number of microorganisms that can provide different life-support functions, including nutrient acquisition and protection against (a)biotic stresses like drought or pathogen attack Here, the diversity of bacteria living inside plant root tissue was explored with a focus on Actinobacteria, and in particular Streptomyces. Streptomycetes are filamentous bacteria that are commonly found in soil. They were brought into the laboratory for their ability to produce a large diversity of natural products, including many different antibiotics. In plant-associated environments, Streptomyces can be found in the rhizosphere, the endosphere and the phyllosphere. In these niches, they receive nutrients from the plants, feasting on various biopolymers and exudates. In return, the plant may benefit from their presence by enhanced nutrient acquisition, pathogen antagonism and induced systemic resistance To date, however, plant-Streptomyces interactions are not well understood and the mechanisms underlying plant colonization and invasion by Streptomyces remain largely elusive. Also, the chemistry of plant-Streptomyces interactions is yet underexplored, leaving us with a reservoir of untapped natural products that may contribute to solving the problem of emerging antibiotic resistance. Therefore, this research was focused on the aforementioned topics. Show less
