Research bacterial meningitis

Bacterial meningitis is a severe infection of the meninges, most commonly caused by the bacteria Streptococcus pneumoniae. Despite treatment mortality remains high and survivors suffer from long term sequelae. Increasing our knowledge about the onset and development of the disease can lead to ideas for new treatments.

With our clinical research we study the disease course of meningitis and we look for factors that influence outcomes such as mortality and neurological sequelae. For example we study the rol of genetic variation, metabolites and lipids in pneumococcal meningitis. Subsequently, with translation research we try to find the underlying mechanism through which this factors influence disease. To do this we use experimental models of meningitis, such as cells infected with pneumococcal bacteria and models of meningitis in zebrafish or mice. By improving our understanding of the underlying processes of meningitis, we hope to find leads for new treatments for meningitis. 

From genes to treatment

Specific mutations in both human and bacterial genes can influence the course of bacterial meningitis.  For example, due to a mutation a gene that is crucial for fighting the infection might not work properly. Or a mutationt can make a gene hyperactive, leading to a defective immune response.

To study the effect of genetic variation in humans on the course of the disease, we use in vitro (cell lines) and in vivo research models (animal models). For example, we can use cell lines to test how cells respond to the pneumococcus and which genes and proteins are involved. We can then study these genes further in mouse models, where we can switch off and/or restore function of the gene of interest and investigate the effects in the setting of meningitis.

In addition to genetic variation in humans, we are also interested in the genetic variation of bacteria. We have identified multiple genes that may be important for pneumococcal virulence. In our zebrafish model we investigate the role of these genes on the course of meningitis and the interaction with the immune system.