Resorantel: a dual-targeting therapeutic with potent efficacy against Staphylococcus aureus with low potential for drug resistance

Methicillin-resistant Staphylococcus aureus (MRSA) has emerged as a significant public health concern. The biofilm formation capability of MRSA is often associated with high levels of antimicrobial resistance. Therefore, the development of novel therapeutic strategies to combat MRSA is urgently warranted. By drug repurposing, resorantel, originally developed as an antiparasitic agent, has demonstrated significantly bactericidal activity against MRSA and its biofilms with effectively inhibitory activity against the emergence of drug resistance. Furthermore, resorantel displayed significant in vivo antibacterial efficacy in both topic and systemic infection models. Mechanistic investigations employing transcriptomics, fluorescent probes, molecular dynamics simulations, and surface plasmon resonance analysis revealed that proton motive force and MurB are likely the potential targets of resorantel. Collectively, this study identifies resorantel as a promising novel antimicrobial agent with potential for use in the treatment of MRSA and its biofilm-related infections.