Phage-Nanoparticle Cocktails as a Novel Antibacterial Approach: Synergistic Effects of Bacteriophages and Green-Synthesized Silver Nanoparticles

Abstract

Bacteriophages have emerged as promising natural antibacterial agents, offering a targeted approach to combating bacterial infections. While phage-antibiotic cocktails are widely explored to enhance antibacterial efficacy and prevent resistance, research on phage-nanoparticle combinations remains limited. However, antibiotic resistance continues to rise, necessitating alternative strategies. Combining bacteriophages with nanoparticles presents a novel approach that could enhance antibacterial potency while reducing the risk of resistance, yet studies in this area are still scarce. We explore the synergy between green tea extract-capped silver nanoparticles (G-TeaNPs) and bacteriophages in combating pathogenic bacteria (Staphylococcus aureus, Salmonella enterica). G-TeaNPs show no antiphage activity, ensuring compatibility in phage-NP formulations. These combinations significantly reduce bacterial counts in a short time (only 3 hours), e.g., S. aureus survival is around 30% after incubations with just 0.001 mg/mL of G-TeaNPs, with G-TeaNPs and phages alone result in around 80% and 70% survival, respectively. Cytotoxicity tests against eukaryotic 3T3 NIH fibroblast cells confirmed biocompatibility at effective concentrations. Additionally, we examine G-TeaNPs impact on the free-living protist Acanthamoeba castellanii. Both green tea extract and G-TeaNPs can reduce A. castellanii cell counts by 80%, but only at concentrations larger than 10 mg/mL. Microscopy revealed nanoparticle uptake by amoebae, causing intracellular accumulation and vacuolization, while green tea extract induced similar changes without uptake. Our findings highlight G-TeaNPs as safe, effective agents in phage-nanoparticle antibacterial formulations with dual antimicrobial and amoebicidal properties for therapeutic and environmental applications.