Zinc oxide nanoparticles reduce biofilm formation, synergize antibiotics action and attenuate Staphylococcus aureus virulence in host; an important message to clinicians

Abstract

Background: Biofilm-related infections are difficult to be treated because of higher resistance to antimicrobial agents. Current study aims to characterize the influence of zinc oxide nanoparticles (ZnO-NPs) on both S. aureus susceptibility to antibiotics and pathogenesis. Methods: The influence of ZnO-NPs on biofilm formation by S. aureus was characterized by the crystal violet and tube assay. The synergistic effect of ZnO-NPs in combination with antibiotics on S. aureus was characterized using the checkerboard method. The effect of ZnO-NPs on S. aureus cell surface hydrophobicity and blood hemolysis was investigated. RT-qPCR was used to investigate the effect of ZnO-NPs on the expression of biofilm related genes (icaA, icaR and sarA), katA and sigB. The impact of ZnO-NPs on S. aureus pathogenesis was evaluated using mice infection model. Results: ZnO-NPs exhibited a good antibiofilm activity against S. aureus. The findings indicate a synergistic antibiofilm effect of combination between ZnO-NPs and tested antibiotics. ZnO-NPs were capable of decreasing S. aureus cell surface hydrophobicity which could account for observed decrease in bacterial biofilm forming capacity. Moreover, ZnO-NPs-treated bacteria exhibited a significant decrease in blood hemolysis relative to control untreated S. aureus. The expression of biofilm related genes was significantly repressed in ZnO-NPs treated bacteria as compared to untreated cells. Finally, the effect of ZnO-NPs on S. aureus pathogenesis was investigated using mice infection model where ZnO-NPs accelerated healing of wounds in mice as compared to control untreated mice. Conclusions: Present data support the efficiency of ZnO-NPs as antibiofilm agent in treatment of S. aureus infections. This study recommends the incorporation of ZnO-NPs as adjuvant with other antibiotics targeting S. aureus based on the promising findings obtained herein in order to control infection with this pathogen.