Molecular Bacteriology

Research on bacterial pathogens addresses the mechanisms that lead to virulence and antibiotic resistance of Staphylococcus aureus and Streptococcus pneumoniae in order to identify novel targets for preventive or therapeutic interventions with novel anti-microbial agents, human monoclonal antibodies or vaccines. An important aspect is the analysis of host-pathogen interactions for which in vitro, ex vivo and in vivo model systems are applied.

The ecological studies address the dynamics of the human gut microbiota and interactions between bacteria and their host, not only in relation to disease, but also in response to interventions with antibiotics, prebiotics or probiotics.

A major theme within all bacteriological studies is the analysis of the secretome, which includes all proteins exported to the cell surface and host milieu. This is important, because the secretome is the main reservoir of compounds that influence human health in negative or positive ways. To obtain deeper insights in the roles of the secretome in bacterial fitness, growth, survival and antibiosis, the non-pathogenic model bacterium Bacillus subtilis is studied by means of Systems Biology approaches.

Epithelial and endothelial cells form mechanical barriers that maintain the integrity of body compartments. Extracellular bacterial often traverse these boundaries, resulting in invasion of the deeper tissues and concomitant disease. How the bacteria cross these barriers is still poorly understood. To study pathogen translocation over endothelial cell layers, We use the Gram-positive bacterium Streptococcus pneumoniae as a model system. Streptococcus pneumoniae (the pneumococcus) is a common cause of respiratory disease and serious invasive diseases such as pneumonia, sepsis and meningitis. A prerequisite for invasive disease is entry of the bacteria into the bloodstream or translocation of the blood-brain barrier, both of which require Streptococcus pneumoniae to cross endothelial cell layers. Although Streptococcus pneumoniae is regarded as an extracellular pathogen, it invades eukaryotic cells both in vitro and in vivo. Invasion is thought to be the first step in a specific and receptor-mediated intracellular process of Streptococcus pneumoniae traversal over eukaryotic cell layers that significantly contributes to the pathogenesis of the bacterium. Research in my group is aimed at understanding the interaction between the bacteria and the host cells, in particular endothelial cells.

Our main research topics 

• Identification of S. pneumoniae genes needed for invasion of, survival in and translocation of endothelial and epithelial cells
• Study of the entry mechanisms of S. pneumoniae into endothelial cells Study of the interaction of S. pneumoniae with the endothelium of the brain in vivo Role of oxidative stress survival in invasive disease
• Relation between the amount of capsule, metabolism and the interaction with eukaryotic cells