AUTHOR=She Pengfei , Li Shijia , Zhou Linying , Liu Yaqian , Xu Lanlan , Hussain Zubair , Li Yimin , Li Zehao , Liu Shasha , Wu Yong 

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

JOURNAL=Frontiers in Microbiology

VOLUME=12

YEAR=2022

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2021.790686

DOI=10.3389/fmicb.2021.790686

ISSN=1664-302X

ABSTRACT=<p>Because of the excessive use of antibiotics, methicillin-resistant <italic>Staphylococcus aureus</italic> (MRSA) has become prevalent worldwide. Moreover, the formation of <italic>S. aureus</italic> 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 <italic>S. aureus</italic> and its biofilms. Through our mechanistic studies, EP was found to interfere with proton motive force in <italic>S. aureus</italic>. The <italic>in vivo</italic> 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 <italic>in vivo</italic> 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.</p>