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

Abstract

To evaluate potential pathomechanisms in the induction of infective endocarditis (IE), 34 Staphylococcus aureus ( S. aureus ) isolates, collected from patients with S. aureus endocarditis and from healthy individuals were investigated both in vitro and in vivo. S. aureus isolates were tested in vitro for 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. aureus to induce vegetations on the aortic valves in vivo . In an animal model of IE valvular conspicuity was assessed by in vivo magnetic resonance imaging at 9.4 T, histology and enrichment gene expression analysis. All S. aureus isolates tested in vivo caused a reliable infection and inflammation of the aortic valves, but could not be differentiated and categorized according to the measured in vitro virulence profiles and cytotoxicity. Results from in vitro assays 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. aureus infective endocarditis would offer novel possibilities for the development of therapeutic strategies and specific diagnostic imaging markers.

Infective Endocarditis in High-Income Countries

“…Recently, Schwartz et al offered a very precise evaluation of the potential pathomechanisms involved in inducing infective endocarditis. The analysis was performed by studying 34 isolates of S. aureus , collected from patients with S. aureus endocarditis and from healthy individuals in both in vitro and in vivo models [ 114 ].…”

“…S. aureus isolates were tested in vitro for their cytotoxicity, the potential for invasion, and interaction with platelets. All strains of S. aureus isolated and tested in vivo revealed the ability to cause IE and the inflammatory response associated with the aortic valve’s injuries; however, investigators were unable to differentiate and classify IE and inflammation based on the measurement of in vitro virulence profiles and cytotoxicity [ 114 ].…”

“…Investigators, therefore, suggest that the pathogenic capacity of bacteria does not confer a uniform response, and comprehensive approaches to host–pathogen interactions are required for its evaluation. Furthermore, this approach offers the possibility to study the corresponding immune pathways in order to highlight the differences in the host–pathogen interaction [ 114 ].…”

“…Considering the etiology of Staphylococcus aureus -induced infective endocarditis, Schwarz et al opened a window to reach a better understanding of the interaction between virulence factors and immune response in S. aureus -borne infective endocarditis, to offer new possibilities for the development of therapeutic strategies and specific diagnostic imaging markers [ 114 ].…”

Pathophysiology of Infective Endocarditis in High-Income Countries

“…The findings of Lockhart's study suggest that although amoxicillin has a significant impact on bacteraemia resulting from single tooth extraction, however, as the increased frequency of oral hygiene is exerted by tooth brushing, the latter may represent a greater threat to people at risk of infective endocarditis. [115] Landmark RCT of Lockhart et al substantially supported that oral hygiene and gingival disease indexes were associated significantly with the development of infective endocarditis-related bacteremia after toothbrushing.…”