Repurposing Eltrombopag as an Antimicrobial Agent Against Methicillin-Resistant Staphylococcus aureus

Abstract

Because of the excessive use of antibiotics, methicillin-resistant Staphylococcus aureus (MRSA) has become prevalent worldwide. Moreover, the formation of S. aureus biofilms often cause persistence and relapse of infections. Thus, the discovery of antibiotics with excellent antimicrobial and anti-biofilm activities is urgently needed. In the present study, eltrombopag (EP), a classic thrombopoietin receptor agonist, exhibited potential antimicrobial activity against S. aureus and its biofilms. Through our mechanistic studies, EP was found to interfere with proton motive force in S. aureus. The in vivo anti-infective efficacy of EP was further confirmed in the wound infection model, thigh infection model and peritonitis model by MRSA infection. In addition, the cytotoxicity of EP against mammalian cells and the in vivo toxicity of EP in animal models were not observed at the tested concentrations. Collectively, these results indicate that EP could be considered a potential novel antimicrobial agent against recalcitrant infections caused by MRSA.