biostudies-literatureUnknown12She PNatural Science Foundation of Hunan ProvinceNational Natural Science Foundation of ChinaBecause of the excessive use of antibiotics, methicillin-resistant <i>Staphylococcus aureus</i> (MRSA) has become prevalent worldwide. Moreover, the formation of <i>S. aureus</i> 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 <i>S. aureus</i> and its biofilms. Through our mechanistic studies, EP was found to interfere with proton motive force in <i>S. aureus</i>. The <i>in vivo</i> 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 <i>in vivo</i> 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.Frontiers in microbiology790686https://www.ebi.ac.uk/biostudies/studies/S-EPMC8819062biostudies-literatureRepurposing Eltrombopag as an Antimicrobial Agent Against Methicillin-Resistant <i>Staphylococcus aureus</i>.PMC8819062Xu LZhou LLiu YShe PLi YLi ZLi SHussain ZLiu SWu YfalseRepurposing Eltrombopag as an Antimicrobial Agent Against Methicillin-Resistant <i>Staphylococcus aureus</i>.Because of the excessive use of antibiotics, methicillin-resistant <i>Staphylococcus aureus</i> (MRSA) has become prevalent worldwide. Moreover, the formation of <i>S. aureus</i> 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 <i>S. aureus</i> and its biofilms. Through our mechanistic studies, EP was found to interfere with proton motive force in <i>S. aureus</i>. The <i>in vivo</i> 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 <i>in vivo</i> 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.2021-01-01T00:00:00Z20212025-04-25T22:30:59.169Z2025-04-06T09:04:29.438ZS-EPMC88190623514069310.3389/fmicb.2021.790686