Synergistic ROS-Associated Antimicrobial Activity of Silver Nanoparticles and Gentamicin Against Staphylococcus epidermidis .

Introduction: Increasing bacteria resistance to antibiotics is a major problem of healthcare system. There is a need for solutions that broaden the spectrum of bactericidal agents improving the efficacy of commonly used antibiotics. One of the promising directions of search are silver nanoparticles (obtained by different methods and displaying diversified physical and chemical properties), and their combination with antibiotics. Purpose: In this study, we tested the role of reactive oxygen species in the mechanism of synergistic antibacterial activity of gentamicin and Tween-stabilized silver nanoparticles against gentamicin-resistant clinical strains of Staphylococcus epidermidis. Methods: Synergistic bactericidal activity of gentamicin and silver nanoparticles stabilized with non-ionic detergent (Tween 80) was tested by the checkerboard titration method on microtiter plates. Detection of reactive oxygen species was based on the chemiluminescence of luminol. Results: Hydrophilic non-ionic surface functionalization of silver nanoparticles enabled the existence of non-aggregated active nanoparticles in a complex bacterial culture medium. Tween-stabilized silver nanoparticles in combination with gentamicin exhibited bactericidal activity against multidrug-resistant biofilm forming clinical strains of Staphylococcus epidermidis. A synergistic effect significantly decreased the minimal inhibitory concentration of gentamicin (the antibiotic with numerous undesirable effects). Gentamicin significantly enhanced the generation of reactive oxygen species by silver nanoparticles. Conclusion: Generation of reactive oxygen species by Tween-coated metallic silver nanoparticles was significantly enhanced by gentamicin, confirming the hypothesis of oxidative-associated mechanism of the synergistic antibacterial effect of the gentamicin-silver nanoparticles complex.