Le mardi 3 décembre 2024, Madame Kirsten LEETEN, titulaire d’un Master en sciences biomédicales (KUL) et d’un Certificat de formation à la recherche en sciences biomédicales et pharmaceutiques, présentera l'examen en vue de l'obtention du grade de Doctorat en Sciences biomédicales et pharmaceutiques, sous la direction de Madame Cécile OURY et de Monsieur Patrizio LANCELLOTTI. 

Cette épreuve consistera en la défense publique d'une thèse intitulée :  "Unravelling the antibacterial mechanism of action of ticagrelor and its activity against Staphylococcus aureus infective endocarditis". 

Le jury sera composé de :

Marie-Pierre HAYETTE (Présidente), Christelle LECUT (Secrétaire), Dorte FREES (Univ. Copenhagen), Patrizio LANCELLOTTI, Cécile OURY, Bernard PIROTTE, Thomas VANASSCHE (KUL)

Résumé de la thèse

Multidrug-resistant bacteria contribute to various infectious diseases including the challenging disease infective endocarditis. The escalating prevalence of infections caused by antibacterial-resistant strains urges the need to explore new therapeutic strategies. A drug that has garnered interest is the P2Y12 antagonist ticagrelor, which was reported to have antibacterial properties against Gram-positive and resistant Gram-positive bacteria. 

We investigated the antibacterial mechanism of action of ticagrelor in Staphylococcus aureus and its activity against Staphylococcus aureus infective endocarditis. Our findings demonstrate that ticagrelor exerts a dose-dependent disruptive effect on the bacterial membrane, by interacting with predominant lipids of the membrane including phosphatidylglycerol, cardiolipin, and diacylglycerol. Notably, ticagrelor retains its antibacterial activity against multidrug-resistant staphylococci including daptomycin- and vancomycin-resistant strains and enhances the antibacterial activity of these last-resort antibiotics. 

We further revealed that a conventional dose of ticagrelor reduces bacterial virulence and downregulates the expression of key virulence regulators, including components of the accessory gene regulator system. Lastly, we describe ticagrelor to reduce infective endocarditis development in an inflammation induced mouse model, which could be partly contributed to the diminished bacterial virulence. Our findings support the therapeutic potential of ticagrelor as a prophylactic antibacterial agent in high-risk cardiovascular patients.