Repurposed Fenoprofen Targeting SaeR Attenuates <i>Staphylococcus aureus</i> Virulence in Implant-Associated Infections

Implant-associated infections (IAIs) caused by S. aureus can result in serious challenges after orthopedic surgery. Due to biofilm formation and antibiotic resistance, this refractory infection is highly prevalent, finding drugs attenuate bacterial virulence becoming a rational alternative strategy. In aureus, the SaeRS two-component system (TCS) plays key role production of over 20 factors pathogenesis bacterium. Here, conducting structure-based virtual screening against SaeR, we identified that fenoprofen, USA Food Drug Administration (FDA)-approved nonsteroid anti-inflammatory drug (NSAID), had excellent inhibitory potency response regulator SaeR protein. We showed fenoprofen attenuated without resistance. addition, it was helpful relieving osteolysis restoring walking ability mice vitro implant-associated models. More importantly, treatment suppressed changed structure, which form loose porous biofilms were more vulnerable infiltration elimination leukocytes. Our results reveal potent antivirulence agent with potential value clinical applications target infections.