Protective Effect of Ticagrelor Against Infective Endocarditis Induced by Virulent Staphylococcus aureus in Mice
Cécile Oury, Severien Meyers, Nicolas Jacques, Kirsten Leeten, Zheshen Jiang, Lucia Musumeci, Marleen Lox, Margaux Debuisson, Eric Goffin, Bernard Pirotte, Philippe Delvenne, Alain Nchimi, Cédric Hubert, Mélanie Heptia, Philippe Hubert, Marijke J.E. Kuijpers, Thomas Vanassche, Kimberly Martinod, Peter Verhamme, Patrizio Lancellotti
Abstract
In addition to its potent antiplatelet activity, ticagrelor possesses antibacterial properties against gram-positive bacteria. We wondered whether the typical clinical dosage of ticagrelor could prevent the development of infective endocarditis caused by highly virulent Staphylococcus aureus. Ticagrelor prevented vegetation formation in a mouse model of inflammation-induced endocarditis. The dosage achieved in patients under ticagrelor therapy altered bacterial toxin production and adherence on activated endothelial cells, thereby mitigating bacterial virulence. Besides the previously described bactericidal activity at high doses, ticagrelor at typical clinical doses possesses antivirulence activity against S aureus. Ticagrelor antiplatelet activity further interferes with the interplay between platelets and bacteria.