Host-pathogen interactions of clinical S. aureusisolates to induce infective endocarditis

ABSTRACTTo evaluate potential pathomechanisms in the induction of infective endocarditis (IE), 34 Staphylococcus aureus(S. aureus) isolates, collected from patients with S. aureusendocarditis and from healthy individuals were investigated both in vitroand in vivo. S. aureusisolates were tested in vitrofor their cytotoxicity, invasion and the association with platelets. Virulence factor expression profiles and cellular response were additionally investigated and tested for correlation with the ability of S. aureusto induce vegetations on the aortic valves in vivo. In an animal model of IE valvular conspicuity was assessed by in vivomagnetic resonance imaging at 9.4 T, histology and enrichment gene expression analysis. All S. aureusisolates tested in vivocaused a reliable infection and inflammation of the aortic valves, but could not be differentiated and categorized according to the measured in vitrovirulence profiles and cytotoxicity. Results from in vitroassays did not correlate with the severity of IE. However, the isolates differed substantially in the activation and inhibition of pathways connected to the extracellular matrix and inflammatory response. Thus, comprehensive approaches of host-pathogen interactions and corresponding immune pathways are needed for the evaluation of the pathogenic capacity of bacteria. An improved understanding of the interaction between virulence factors and immune response in S. aureusinfective endocarditis would offer novel possibilities for the development of therapeutic strategies and specific diagnostic imaging markers.