Cu-Bearing Antibacterial Stainless Steel Potentiates Antibiotic Sensitivity to Combat Methicillin-resistant Staphylococcus aureus

Treating biofilm formation-induced implant-associated infections is challenging, and they often lead to antimicrobial resistance, which significantly contributes to human mortality worldwide. Consequently, an increase in antibiotic resistance has warranted the development of more effective strategies to combat the drug-resistant bacterial infections. Hence, this study aimed to develop an antibacterial metal implant material (Cu-bearing 316L stainless steel) as a quorum-sensing inhibitor (QSI) for reversing drug resistance in resistant bacteria. Notably, RNA sequencing results revealed that 316L-Cu SS could interfere with the formation of multidrug resistance barriers of Methicillin-resistant Staphylococcus aureus (MRSA), including biofilm development and metabolism, by inhibiting quorum-sensing signals. Furthermore, the resistance of MRSA to ciprofloxacin (CIP) was reversed, with up to a 67% decline in minimum bactericidal concentration. Subsequently, a QSI–CIP combination strategy was developed for synergistic action against MRSA, which achieved almost complete elimination of MRSA at low antibiotic dosage. Overall, the findings of this study present the novel antibacterial implant material as a lead QSI, highlighting the potential of adjunctive pathoblocker-mediated therapy against infections and providing a long-term activity to address the intractable challenge of drug-resistant bacteria with enhanced sustainability.