Staphylococcus aureus infection of endothelial cells

• Applicant: Professor Dr. Andreas Peschel
• Subject Area: Parasitology and Biology of Tropical Infectious Disease Pathogens
• Term: from 2002 to 2011
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 5389431

Staphylococcus aureus is one of the most prevalent causes of blood stream infections. Endovascular S. aureus diseases such as endocarditis and the frequent induction of metastatic infections involve adherence to endothelial cells, induction of phagocytosis and intracellular persistence, followed by activation and damage of endothelial cells. The factors mediating adherence and uptake and modulating endothelial functions are still elusive. Fibronectin-binding proteins and fibronectin have previously been identified as crucial determinants for interactions with endothelial cells. Our data reveal now an equally important role of teichoic acids, staphylococcal cell wall polymers, as adhesins for binding to endothelial cells. Lipoteichoic acids are also important activators of cytokine production and surface protein upregulation in endothelial cells. We want to use our set of teichoic acids mutants and of strains deficient in fibronectin binding proteins to characterize the contribution of the various S. aureus factors to binding, uptake into, and activation of endothelial cells. The Rho GTPase-inactivating S. aureus toxin EDIN has been implicated in modulation of endothelial functions. While the previous experiments were carried out with purified EDIN, we intend to generate defined S. aureus EDIN knock-out and knock-in mutants and analyze the impact of this toxin on activation of endothelial cells and on the ability of S. aureus to persist within or damage endothelial cells in cell culture and animal experiments.

• DFG Programme: Priority Programmes
• Subproject of: SPP 1130: Infections of the Endothelium
• Participating Person: Dr. Christopher Weidenmaier