PhD ceremony Ms. M.M. van der Kooi-Pol: In vivo and in vitro profiling of global interactions between Staphylococcus aureus and its human host

PhD ceremony: Ms. M.M. van der Kooi-Pol, 14.30 uur, Academiegebouw, Broerstraat 5, Groningen

Dissertation: In vivo and in vitro profiling of global interactions between Staphylococcus aureus and its human host

Promotor(s): prof. J.M. van Dijl

Faculty: Medical Sciences

The opportunistic pathogen Staphylococcus aureus has become a major threat for human health and well-being by developing resistance to antibiotics, and by its fast evolution into new lineages that rapidly spread within the healthy human population. This calls for the development of active or passive immunization strategies to prevent and cure staphylococcal diseases. These novel strategies to combat S. aureus must be based on an integrated approach that requires the identification of invariant and immune-dominant targets. The identification of such targets requires (i) in-depth analyses on the localization of proteins and other compounds to the staphylococcal cell surface and (ii) a thorough understanding of the human immune responses to these cell surface-exposed compounds. The research described in this thesis was therefore aimed at defining the interactions between S. aureus and its human host in vivo and in vitro. In particular, studies of immune responses elicited by S. aureus colonization in patients with the genetic blistering disease epidermolysis bullosa (EB) revealed several highly immunogenic staphylococcal proteins and their epitopes. In addition, in vitro studies have pinpointed various mechanisms that are important for the cell surface exposure of different S. aureus proteins that are known to be involved in staphylococcal infections. Taken together, the findings reported in this thesis contribute to a better understanding of the interactions between humans and S. aureus during colonization and infection. The main challenges for future research now lie in the translation of the present findings into novel strategies for antistaphylococcal therapy.