Host-microbe interactions as elicitors of cryptic antibiotics in actinomycetes and spread of antimicrobial resistance under low antibiotic stress
Group and collaboration
Herman Spaink & Gilles van Wezel - Institute of Biology Leiden University
PhD student: Doris van Bergeijk
In this project, we will analyse the role of host-pathogen interactions in the control of natural product biosynthesis by actinomycetes, and establish the role of host-specific signalling in the control of antibiotic production by actinomycetes. In addition, using a metagenome approach, we will analyse the biosynthetic potential of the host microbiome and also investigate the role of horizontal gene transfer (HGT) in spreading antimicrobial resistance under normal conditions, during antibiotic challenge and during colonization of a host. As disease models we will use the well-established zebrafish larval model for mycobacterial infection, and infection of the mammalian lung by Pseudomonas aeruginosa. Since in animals we anticipate that the endogenous microbiome is important to modulate the strength of signalling to microbes a zebrafish gnotobiotic model is used to analyse the complexity involved in interactions of actinomycetes with animal cells.
- Uncovering the host-specific signals that control actinomycete gene function during bacterial-host interactions in zebrafish- and human-derived cells and (lung) organoids.
- Metagenomic analysis of the lung metagenome
- Metagenomic analysis of HGT of resistance genes during different antibiotic challenge regimes in controlled microcosms and in zebrafish larvae.
- Study the effect of molecules/hormones discovered under (1) as elicitors of cryptic antibiotic biosynthetic gene clusters of actinomycetes.
- Identify the bioactive compounds elicited under (3) and elucidate their chemical structure and mode of action.
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.’