Phage/nanoparticle cocktails for a biocompatible and environmentally friendly antibacterial therapy

Antibiotic resistance continues to rise, necessitating alternative strategies. Bacteriophages have emerged as promising natural antibacterial agents, offering a targeted approach to combating bacterial infections. Combining bacteriophages with nanoparticles presents a novel approach that could enhance antibacterial potency while reducing the risk of resistance. While phage/antibiotic cocktails are widely explored to enhance antibacterial efficacy and prevent resistance, research on phage/nanoparticle combinations remains limited. We explore the synergy between green tea extract-capped silver nanoparticles (G-TeaNPs) and bacteriophages in combating pathogenic bacteria (methicillin-resistant Staphylococcus aureus, Salmonella enterica). G-TeaNPs show minimal antiphage activity, ensuring compatibility in phage-NP formulations. These combinations significantly reduce bacterial counts in a short time (only 3 h), e.g., S. aureus survival is around 30% after incubation with just 0.001 mg/mL of G-TeaNPs, while G-TeaNPs and phages alone result in around 80% and 70% survival, respectively. Cytotoxicity tests against eukaryotic 3T3 NIH fibroblast cells confirm 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 high concentrations. 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. KEYPOINTS: • Silver nanoparticles synthesized with tea extracts (G-TeaNPs) have a minimal effect on the tested viruses. • Combining G-TeaNP with bacteriophages offers new-generation antibacterial cocktails. • Green tea extracts and AgNPs present concentration-dependent anti-amoebic activity.