Journal Article

Ticagrelor alters the membrane of Staphylococcus aureus and enhances the activity of vancomycin and daptomycin without eliciting cross-resistance

Piel, Géraldine, Penoy, Noémie, Joris, Bernard, Melo, Sofia, Amoroso, Ana, Sánchez-López, Elena, Slavetinsky, Christoph J., Straetener, Jan, Pirotte, Bernard, Lancellotti, Patrizio, Oury, Cécile, Musumeci, Lucia, Verlaine, Olivier, Jacques, Nicolas, Frees, Dorte, Henriksen, Camilla, Schneider, Dana C., Brötz-Oesterhelt, Heike, Leeten, Kirsten, Putters, Florence, Giera, Martin, Esquembre, Lidia Alejo, Goffin, Eric

2024

Overview

Infections with multidrug-resistant bacteria pose a major healthcare problem with an urgent need for novel treatment options. The antiplatelet drug ticagrelor possesses antibacterial activity against Gram-positive bacteria including methicillin-resistant and vancomycin-resistant Staphylococcus aureus strains. We report a unique, dose-dependent, antibacterial mechanism of action of ticagrelor, which alters the properties and integrity of the bacterial cytoplasmic membrane. Ticagrelor retains activity against multidrug-resistant staphylococci, including isolates carrying the most common in vivo selected daptomycin resistance mutations and vancomycin-intermediate Staphylococcus aureus . Our data support the use of ticagrelor as adjunct therapy against multidrug-resistant strains. Because of the presence of multiple non-protein targets of this drug within the bacterial membrane, resistance development is expected to be slow. All these findings corroborate the accumulating observational clinical evidence for a beneficial anti-bacterial effect of ticagrelor in cardiovascular patients in need of such treatment.

• Publisher: American Society for Microbiology
• Subject: Acute coronary syndromes / Anti-Bacterial Agents - pharmacology / Antibacterial activity / Antibiotics / Bacillus subtilis / Bacillus subtilis - drug effects / Bacillus subtilis - genetics / Bacteria / Bacterial infections / Biomarkers / Cardiolipin / Cell Membrane - drug effects / Cell size / Cross-resistance / Cytoplasmic membranes / Daptomycin / Daptomycin - pharmacology / Depolarization / Diglycerides / drug discovery / Drug dosages / drug interactions / Drug resistance / Drug Resistance, Multiple, Bacterial / Drug Synergism / Gram-positive bacteria / Health care / Humans / Life sciences / Lipids / Localization / Membrane potential / Methicillin / Methicillin-Resistant Staphylococcus aureus - drug effects / Methicillin-Resistant Staphylococcus aureus - genetics / Microbial Sensitivity Tests / Microbiologie / Microbiology / Microscopy / Multidrug resistance / Mutation / Patients / Peptidoglycans / Pharmacology / Phosphatidylglycerol / platelets / Proteins / Research Article / Sciences du vivant / Staphylococcus aureus / Staphylococcus aureus - drug effects / Staphylococcus aureus - genetics / Staphylococcus infections / Strains (organisms) / Ticagrelor - pharmacology / Vancomycin / Vancomycin - pharmacology / Whole genome sequencing