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

doi:10.1016/j.jacbts.2023.02.003

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

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

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.

Original language	English
Pages (from-to)	1439-1453
Number of pages	15
Journal	JACC: Basic to Translational Science
Volume	8
Issue number	11
DOIs	https://doi.org/10.1016/j.jacbts.2023.02.003
Publication status	Published - 1 Nov 2023

Keywords

bacterial virulence
infective endocarditis
Staphylococcus aureus
ticagrelor

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Oury, C., Meyers, S., Jacques, N., Leeten, K., Jiang, Z., Musumeci, L., Lox, M., Debuisson, M., Goffin, E., Pirotte, B., Delvenne, P., Nchimi, A., Hubert, C., Heptia, M., Hubert, P., Kuijpers, M. J. E., Vanassche, T., Martinod, K., Verhamme, P., & Lancellotti, P. (2023). Protective Effect of Ticagrelor Against Infective Endocarditis Induced by Virulent Staphylococcus aureus in Mice. JACC: Basic to Translational Science, 8(11), 1439-1453. https://doi.org/10.1016/j.jacbts.2023.02.003

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title = "Protective Effect of Ticagrelor Against Infective Endocarditis Induced by Virulent Staphylococcus aureus in Mice",

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.",

keywords = "bacterial virulence, infective endocarditis, Staphylococcus aureus, ticagrelor",

author = "C{\'e}cile Oury and Severien Meyers and Nicolas Jacques and Kirsten Leeten and Zheshen Jiang and Lucia Musumeci and Marleen Lox and Margaux Debuisson and Eric Goffin and Bernard Pirotte and Philippe Delvenne and Alain Nchimi and C{\'e}dric Hubert and M{\'e}lanie Heptia and Philippe Hubert and Kuijpers, \{Marijke J.E.\} and Thomas Vanassche and Kimberly Martinod and Peter Verhamme and Patrizio Lancellotti",

note = "Funding Information: The JE2 ?Hla is a kind gift from Dorte Frees. ?vwb, ?coa, and ?vwb?coa JE2 strains are a kind gift from Dominique Missiakis. The authors thank the GIGA Institute for access to Biosafety level 2 facilities. Publisher Copyright: {\textcopyright} 2023 The Authors",

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doi = "10.1016/j.jacbts.2023.02.003",

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Oury, C, Meyers, S, Jacques, N, Leeten, K, Jiang, Z, Musumeci, L, Lox, M, Debuisson, M, Goffin, E, Pirotte, B, Delvenne, P, Nchimi, A, Hubert, C, Heptia, M, Hubert, P, Kuijpers, MJE, Vanassche, T, Martinod, K, Verhamme, P & Lancellotti, P 2023, 'Protective Effect of Ticagrelor Against Infective Endocarditis Induced by Virulent Staphylococcus aureus in Mice', JACC: Basic to Translational Science, vol. 8, no. 11, pp. 1439-1453. https://doi.org/10.1016/j.jacbts.2023.02.003

TY - JOUR

T1 - Protective Effect of Ticagrelor Against Infective Endocarditis Induced by Virulent Staphylococcus aureus in Mice

AU - Oury, Cécile

AU - Meyers, Severien

AU - Jacques, Nicolas

AU - Leeten, Kirsten

AU - Jiang, Zheshen

AU - Musumeci, Lucia

AU - Lox, Marleen

AU - Debuisson, Margaux

AU - Goffin, Eric

AU - Pirotte, Bernard

AU - Delvenne, Philippe

AU - Nchimi, Alain

AU - Hubert, Cédric

AU - Heptia, Mélanie

AU - Hubert, Philippe

AU - Kuijpers, Marijke J.E.

AU - Vanassche, Thomas

AU - Martinod, Kimberly

AU - Verhamme, Peter

AU - Lancellotti, Patrizio

N1 - Funding Information: The JE2 ?Hla is a kind gift from Dorte Frees. ?vwb, ?coa, and ?vwb?coa JE2 strains are a kind gift from Dominique Missiakis. The authors thank the GIGA Institute for access to Biosafety level 2 facilities. Publisher Copyright: © 2023 The Authors

PY - 2023/11/1

Y1 - 2023/11/1

N2 - 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.

AB - 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.

KW - bacterial virulence

KW - infective endocarditis

KW - Staphylococcus aureus

KW - ticagrelor

U2 - 10.1016/j.jacbts.2023.02.003

DO - 10.1016/j.jacbts.2023.02.003

M3 - Article

SN - 2452-302X

VL - 8

SP - 1439

EP - 1453

JO - JACC: Basic to Translational Science

JF - JACC: Basic to Translational Science

IS - 11

ER -

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

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Keywords

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