B. pseudomallei and P. aeruginosa are environmental Gram-negative bacteria able to cause chronic and acute infections including blood stream infections that are associated with a high mortality. Our overarching research interest lies in proteins and non-proteinaceous compounds secreted by B. pseudomallei and P. aeruginosa and their role in pathogen-host interaction. Both bacteria display intrinsic resistance to a variety of antibiotics. Advancing our understanding of bacterial factors that promote survival in vivo will facilitate the development of novel treatment strategies.
B. pseudomallei and the type VI secretion system
Burkholderia pseudomallei is a facultative intracellular pathogen able to actively invade non-phagocytic host cells and to survive in phagocytic cells. Following escape into the cytoplasm of host cells B. pseudomallei employs the type VI secretion system 5 (T6SS-5) to induce plasma membrane fusion with an adjacent host cell. This process leads to the formation of multinucleated giant cells and facilitates bacterial access to an uninfected host cell in a direct manner. The T6SS-5 is an essential virulence factor and thus a suitable target for alternative treatment strategies. However, its mechanism of action remains unknown. Using diverse methods such as primary cell culture, protein biochemistry and fluorescence microscopy we aim to identify how the T6SS-5 modulates the host cell to induce giant cell formation and gain insight into the function of the secretion system during infection.
The effect of oxygen limitation on P. aeruginosa virulence
The second main area of research is centered around the influence of oxygen deprivation on P. aeruginosa virulence. During infection of deeper tissue or the lung of cystic fibrosis patients for example, P. aeruginosa is exposed to low oxygen tensions. However, the effect of hypoxic and anaerobic conditions on virulence traits of P. aeruginosa is not well understood. In particular, we focus on proteins whose secretion is stimulated under anoxic conditions. We identified several proteins with predicted enzymatic activity and aim to characterize their activity and role in virulence. In another project we study the mechanisms underlying the oxygen- and c-di-GMP-dependent production of alginate, an exopolysaccharide that provides protection against host immune defenses and antibiotics.