Zebrafish (Danio rerio) is a proven model of human diseases including infectious diseases and offers a powerful combination of genetics with in vivo imaging. We use these traits to study the interaction between a range of bacterial pathogens (Mycobacterium marinum, Streptococcus pneumoniae, Salmonella enterica typhimurium, Escherichia coli, Pseudomonas aeruginosa, and others) and their host.
Our first goal is to identify and understand the diverse virulence factors bacteria need to establish and maintain an infection. Thereby we mainly focus on infections caused by two bacterial species, M. marinum and S. pneumoniae. M. marinum induces a tuberculosis like disease in cold blooded animals like the zebrafish and is a recognized model for studying tuberculosis. By manipulating immune cells, especially macrophages, mycobacteria are able to survive in the host in specialized immune structures called granulomas. The questions we try to answer is what mechanisms and pathways does M. marinum use to interact with the (immune system of the) host and cause disease? Furthermore, we established the zebrafish as a model for meningitis induced by S. pneumoniae orM. marinum. In these studies the emphasis is on the bacterial factors needed for the bacteria to cross the blood brain barrier, to survive in the brain and to manipulate the immune system. Understanding these mechanisms might help us to prevent infection and or improve treatment.
Improving treatment of bacterial infections is our second goal. Since more and more bacterial species become resistant to the currently used antibiotics, there is a need for novel antibiotics that not only kill bacteria but that work in such a way that the bacteria are less likely to become resistant to these new antibiotics. We use the zebrafish model to screen for compounds that work in vivo and are not toxic to an developing embryo. With this model we hope to shorten the time necessary for drug development and increase the likelihood that new drugs will make it to the clinic.