Harnessing Silver Nanoclusters to Combat Staphylococcus aureus in the Era of Antibiotic Resistance

<b>Background/Objectives</b>: In the race to develop new antibiotics to combat multidrug-resistant bacteria, particularly the <i>ESKAPE</i> pathogens which pose a significant threat to public health, silver nanoclusters (AgNCs) have emerged as a promising alternative. This article focuses on the potential of novel silver nanoclusters as an antimicrobial agent against <i>Staphylococcus aureus</i>, a high-priority pathogen known for its ability to cause persistent nosocomial infections and develop protective biofilms. <b>Methods</b>: In this study, we successfully synthesized AgNCs at pH 7 using an eco-friendly photoreduction method with poly acrylic acid (PAA) and poly methacrylic acid (PMAA) as stabilizers. This methodology produced fluorescent AgNCs, demonstrating their stability in aqueous solutions for at least three months and highlighting the effectiveness of PAA and PMAA as stabilizing agents. The AgNCs were incubated with <i>S. aureus</i> suspension, and the antimicrobial capability at different concentrations and times of incubation were determined. Also, the AgNCs hemocompatibility was studied by exposing the clusters to rat blood cells. <b>Results</b>: The in vitro assays revealed that AgNCs capping with PAA or PMAA has antimicrobial activity in low doses (the determination of minimum inhibitory concentration (MIC): 0.2 µg/mL, and the determination of minimum bactericidal concentration (MBC): 2 µg/mL) and without cytotoxicity (hemolysis less than 10%) to rat blood cells until 1 µg/mL. In the presence of both AgNCs (5 µg/mL), bacterial growth was completely inhibited within just 3 h. <b>Conclusions:</b> The findings of this study highlight the potential of silver nanoclusters as effective antimicrobial agents against <i>S. aureus</i>. Their stability, low toxicity, and rapid bactericidal activity make them promising candidates for further development in antimicrobial applications.