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

Oury, Cécile; Meyers, Severien; Jacques, Nicolas; Leeten, Kirsten; Jiang, Zheshen; Musumeci, Lucia; Lox, Marleen; Debuisson, Margaux; Goffin, Eric; Pirotte, Bernard; Delvenne, Philippe; Nchimi, Alain; Hubert, Cédric; Heptia, Mélanie; Hubert, Philippe; Kuijpers, Marijke J.E.; Vanassche, Thomas; Martinod, Kimberly; Verhamme, Peter; Lancellotti, Patrizio

doi:10.1016/j.jacbts.2023.02.003

Cited by 4 publications

(3 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, more recent studies have shown that P2Y12 receptor antagonists such as ticagrelor but not clopidogrel, mitigate Hla-mediated toxic effects on platelets while preserving platelet immune effector function in experimental murine models and in human [ 24 , 28 , 29 ]. Specifically, ticagrelor was shown to interfere with the ability of Hla to initiate platelet aggregation by inhibiting Hla production while not preventing platelet-bacteria bridging by soluble plasma proteins and subsequent platelet aggregation [ 31 ]. Moreover, the study identified that ticagrelor treatment prevented the formation of vegetation in a murine model of SA infective endocarditis.…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, the study identified that ticagrelor treatment prevented the formation of vegetation in a murine model of SA infective endocarditis. Additionally, others have shown that pretreatment of platelets with ticagrelor enhanced human platelet killing of SA in vitro [ 24 , 27 , 31 ]. Taken together, the above findings highlight the complexity of the host–microbe interactions at play that determine the outcome of staphylococcal infections, and in the context of this study, provide further support for applying our ML approach to guide the precision management of SAB.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Machine Learning with Alpha Toxin Phenotype to Predict Clinical Outcome in Patients with Staphylococcus aureus Bloodstream Infection

Beadell,

Nehra,

Gusenov

et al. 2023

Toxins

View full text Add to dashboard Cite

Staphylococcus aureus bloodstream (SAB) infection remains a leading cause of sepsis-related mortality. Yet, current treatment does not account for variable virulence traits that mediate host dysregulated immune response, such as SA α-toxin (Hla)-mediated thrombocytopenia. Here, we applied machine learning (ML) to bacterial growth images combined with platelet count data to predict patient outcomes. We profiled Hla phenotypes of SA isolates collected from patients with bacteremia by taking smartphone images of beta-hemolytic growth on sheep blood agar (SBA). Electronic medical records were reviewed to extract relevant laboratory and clinical data. A convolutional neural network was applied to process the plate image data for input along with day 1 patient platelet count to generate ML-based models that predict thrombocytopenia on day 4 and mortality. A total of 229 patients infected with SA strains exhibiting varying zone sizes of beta-hemolysis on SBA were included. A total of 539 images of bacterial growth on SBA were generated as inputs for model development. One-third of patients developed thrombocytopenia at onset, with an overall mortality rate of 18.8%. The models developed from the ML algorithm showed strong performance (AUC 0.92) for predicting thrombocytopenia on day 4 of infection and modest performance (AUC 0.711) for mortality. Our findings support further development and validation of a proof-of-concept ML application in digital microbiology, with a measure of bacterial virulence factor production that carries prognostic significance and can help guide treatment selection.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Machine Learning with Alpha Toxin Phenotype to Predict Clinical Outcome in Patients with Staphylococcus aureus Bloodstream Infection

Beadell,

Nehra,

Gusenov

et al. 2023

Toxins

View full text Add to dashboard Cite

show abstract

“…This appears to be an effect particularly against gram-positive organisms. For example, in a murine model of S. aureus infective endocarditis, treatment with ticagrelor, but not clopidogrel, reduced vegetation formation compared to drug-free controls, which appeared to be related to effects on bacterial toxin production and endothelial adherence (Oury et al, 2023).…”

Section: At Higher Concentrations Adenosine Primarily Acts On Low-aff...mentioning

confidence: 98%

The role of platelet P2Y₁₂ receptors in inflammation

Parker,

Storey

2023

British J Pharmacology

View full text Add to dashboard Cite

Inflammation is a complex pathophysiological process underlying many clinical conditions. Platelets contribute to the thrombo‐inflammatory response. Platelet P2Y12 amplifies platelet activation, potentiating platelet aggregation, degranulation and shape change. The contents of platelet alpha granules in particular act directly on leucocytes, including mediating platelet‐leucocyte aggregation and activation via platelet P‐selectin. Much evidence for the role of platelet P2Y12 in inflammation comes from studies of P2Y12 inhibitors such as the thienopyridines clopidogrel and prasugrel, and the cyclopentyltriazolopyrimidine ticagrelor, including in animal and human experimental models. These suggest P2Y12 inhibition reduces markers of inflammation with some evidence this reduces incidence of adverse clinical sequelae during inflammatory conditions. Interpretation is complicated by pleiotropic effects such as of thienopyridines on circulating leucocyte numbers and of ticagrelor on adenosine reuptake. The available evidence suggests P2Y12 as a prominent mediator of inflammation and P2Y12 inhibition as a potentially powerful strategy in a broad range of inflammatory conditions.

show abstract

Shikimic Acid Enhances Vancomycin Efficacy in Experimental MRSA-Induced Infective Endocarditis

Lu,

Zhong,

Liu

et al. 2024

Journal of Infection

View full text Add to dashboard Cite

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

Cited by 4 publications

References 37 publications

Machine Learning with Alpha Toxin Phenotype to Predict Clinical Outcome in Patients with Staphylococcus aureus Bloodstream Infection

Machine Learning with Alpha Toxin Phenotype to Predict Clinical Outcome in Patients with Staphylococcus aureus Bloodstream Infection

The role of platelet P2Y₁₂ receptors in inflammation

Shikimic Acid Enhances Vancomycin Efficacy in Experimental MRSA-Induced Infective Endocarditis

Contact Info

Product

Resources

About

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

Cited by 4 publications

References 37 publications

Machine Learning with Alpha Toxin Phenotype to Predict Clinical Outcome in Patients with Staphylococcus aureus Bloodstream Infection

Machine Learning with Alpha Toxin Phenotype to Predict Clinical Outcome in Patients with Staphylococcus aureus Bloodstream Infection

The role of platelet P2Y12 receptors in inflammation

Shikimic Acid Enhances Vancomycin Efficacy in Experimental MRSA-Induced Infective Endocarditis

Contact Info

Product

Resources

About

The role of platelet P2Y₁₂ receptors in inflammation