Due to the widespread abuse of antibiotics, drug resistance in Enterococcus has been increasing. However, the speed of antibiotic discovery cannot keep pace with the acquisition of bacterial resistance. Thus, drug repurposing is a proposed strategy to solve the crises. Lusutrombopag (LP) has been approved as a thrombopoietin receptor agonist by the Food and Drug Administration. This study demonstrated that LP exhibited significant antimicrobial activities against vancomycin-resistant Enterococcus with rare resistance occurrence. Further, LP combined with tobramycin exhibited synergistic antimicrobial effects and against Enterococcus. No or detectable toxicity was observed when using LP. Mechanism studies indicated that the disrupted proton motive force may account for LP's antimicrobial activity. In summary, these results demonstrate that LP has the previously undocumented potential to serve as an antibacterial agent against refractory infections caused by Enterococcus.
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