Host-microbe interactions as elicitors of cryptic antibiotics in actinomycetes and spread of antimicrobial resistance under low antibiotic stress
Group and collaboration
Collaboration: Herman Spaink & Gilles van Wezel (Institute of Biology Leiden University)
PhD student: Doris van Bergeijk
The growing emergence of multidrug-resistant pathogens has increased the need for novel antibiotics. Actinomycetes, in particular Streptomyces, produce a wide variety of natural products important for animal/human health, including anticancer compounds, antifungals, and antibiotics. We are trying to understand the mechanisms behind the antibiotic production of these bacteria. What kind of signals influence their secondary metabolism and how?
Actinomycetes live in close association with different host systems, including plants, insects, marine animals and humans, where they can provide the host with protection against pathogens via the production of bioactive metabolites. Host-specific molecules might serve as signaling molecules from host to microbe, potentially influencing the secondary metabolism. As a model we use (infected) zebrafish larvae, and we have isolated various bacteria from this system that we are currently investigating in terms of their response to different hormones (along with our own actinomycete collection). This highlighted important and hormone-specific changes in growth and production capacity of actinobacteria. We now aim to identify the biosynthesis gene clusters that respond to these hormones.
Another aspect is the change in biosynthetic potential as well as antibiotic resistance over time. We recently had the unique opportunity to isolate and sequence actinomycetes from mammoth stool. This, together with the metagenome data from the stool sample, allows us to study bacteria from the past and analyse the biosynthetic gene clusters and resistance genes that are present. This can give us insight in the way these genes have developed over time. Furthermore, to get more insight in what role actinomycetes can play in the protection of higher organisms, we will study the bioactivity of these isolated bacteria and their potential role in the protection of their host against pathogens.
PhD student interview
‘My interest in antibiotic research started during a microbiology course in the second year of my bachelor. We had to test bacteria from the sewage against different antibiotics and I was shocked by their multi-drug resistance. To me it was clear that we were in need of new antibiotics (or alternatives) and I am very excited that I am now working on a project that will hopefully contribute to the discovery of new antibiotics.’