Protective Effect of Ticagrelor Against Infective Endocarditis Induced by Virulent Staphylococcus aureus in Mice

Area of Science:

• Pharmacology
• Infectious Diseases
• Cardiology

Background:

• Ticagrelor is known for its antiplatelet effects.
• Ticagrelor also exhibits antibacterial properties against Gram-positive bacteria.
• The potential of ticagrelor to prevent infective endocarditis (IE) is unexplored.

Purpose of the Study:

• To investigate if typical clinical doses of ticagrelor can prevent infective endocarditis caused by Staphylococcus aureus.
• To explore the mechanisms underlying ticagrelor's potential anti-IE activity.

Main Methods:

• A mouse model of inflammation-induced endocarditis was utilized.
• Bacterial virulence factors, including toxin production and adherence to endothelial cells, were assessed.
• The interaction between ticagrelor, platelets, and bacteria was examined.

Main Results:

• Ticagrelor effectively prevented vegetation formation in the endocarditis mouse model.
• Clinical doses of ticagrelor reduced Staphylococcus aureus toxin production and adherence to activated endothelial cells.
• Ticagrelor demonstrated antivirulence activity against S. aureus, in addition to its previously known bactericidal effects at high doses.
• Ticagrelor's antiplatelet activity further modulated the interplay between platelets and bacteria.

Conclusions:

• Ticagrelor, at clinically relevant dosages, possesses significant antivirulence properties against Staphylococcus aureus.
• These findings suggest a novel therapeutic potential for ticagrelor in preventing or treating infective endocarditis.
• Ticagrelor's dual action on bacterial virulence and platelet-bacteria interactions offers a unique approach to managing IE.