Phage/nanoparticle cocktails for a biocompatible and environmentally friendly antibacterial therapy
Mateusz Wdowiak, Sada Raza, Mateusz Grotek, Rafał Zbonikowski, Julita Nowakowska, Maria Doligalska, Ning Cai, Zhi Luo, Jan Paczesny
Abstract
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.