Isolating Crucial Steps in Induction of Infective Endocarditis With Preclinical Modeling of Host Pathogen Interaction.
Animal models of Staphylococcus aureus infective endocarditis (IE), especially in rodents, are commonly used to investigate the underlying pathogenesis, disease progression, potential diagnostic approaches, and therapeutic treatment. All these models are based on surgical interventions, and imply valve trauma by placing a polyurethane catheter at the aortic root. While the influence of endothelial damage and inflammation on the induction of IE has been studied intensively, the role of the catheter, as permanent source of bacteremia, and the interplay with bacterial virulence factors during the formation of IE is poorly understood. In our study, we aimed at identifying which set of preconditions is required for induction and formation of IE: (1) tissue injury, (2) permanent presence of bacteria, and (3) presence of the full bacterial repertoire of adhesion proteins. We investigated the manifestation of the disease in different modifications of the animal model, considering different degrees of endothelial damage and the presence or absence of the catheter. In four infection models the induction of IE was assessed by using two bacterial strains with different expression patterns of virulence factors - S. aureus 6850 and Newman. In vivo magnetic resonance imaging showed conspicuous morphological structures on the aortic valves, when an endothelial damage and a continuous bacterial source were present simultaneously. Cellular and inflammatory pathophysiology were characterized additionally by histology, real-time quantitative polymerase chain reaction analysis, and bacterial counts, revealing strain-specific pathogenesis and manifestation of IE, crucially influenced by bacterial adherence and toxicity. The severity of IE was dependent on the degree of endothelial irritation. However, even severe endothelial damage in the absence of a permanent bacterial source resulted in reduced valve infection. The spread of bacteria to other organs was also dependent on the pathogenic profile of the infectious agent.
['Schwarz|Christian|C|', 'Hoerr|Verena|V|', 'Töre|Yasemin|Y|', 'Hösker|Vanessa|V|', 'Hansen|Uwe|U|', 'Van de Vyver|Hélène|H|', 'Niemann|Silke|S|', 'Kuhlmann|Michael T|MT|', 'Jeibmann|Astrid|A|', 'Wildgruber|Moritz|M|', 'Faber|Cornelius|C|']
endocarditis Staphylococcus aureus MRI foreign body mouse model