Mapping the interactions between staphylococcus aureus and host immune cells

PhD ceremony: Ms. M. Miller, 16.15 uur, Academiegebouw, Broerstraat 5, Groningen

Dissertation: Mapping the interactions between staphylococcus aureus and host immune cells

Promotor(s): prof. J.M. van Dijl, prof. M.P. Peppelenbosch

Faculty: Medical Sciences

Staphylococcus aureus is one of the most common human pathogens, and is responsible for a wide range of diseases. S. aureus can be such a successful pathogen, because it secretes an arsenal of virulence factors that assist in host colonization, invasion and tissue destruction. Recent studies showed that the serine/threonine kinase PknB of S. aureus is involved in metabolism and cell wall synthesis. However, the role of PknB in staphylococcal pathogenesis had not been clarified. In this thesis we studied the role of PknB in the interactions between S. aureus and host immune cells. Specifically, the complex interactions between S. aureus and human macrophages were deciphered using kinase profiling, a peptide array-based technology. The results show that staphylococcal PknB has the ability to recognize and phosphorylate human proteins. Also, this kinase is required to provoke inflammatory cytokine production. By studying the host cell responses to PknB-deficient S. aureus cells, it was observed that the activity of host kinases involved in the responses towards S. aureus is significantly decreased if the bacterium fails to produce PknB. Taken together, the data show that S. aureus requires PknB to provoke strong inflammatory responses. This implies that specific PknB inhibitors, which are yet to be developed, may find future applications in combating the fulminant pathology of S. aureus infections.