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PhD defence: Looking at the potential of Filamentous Actinobacteria

On 19 October 2022 Doris van Bergeijk successfully defended her thesis ‘Ecology and genomics of Actinobacteria and their specialised metabolism’ at Leiden University.

Filamentous 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 uncharacterized, 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 her thesis different approaches are described, wherein drug discovery was combined 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.

Link to the thesis: Ecology and genomics of Actinobacteria and their spec

More about the project: Host-microbe interactions as elicitors of cryptic antibiotics in actinomycetes and spread of antimicrobial resistance under low antibiotic stress