Novel silver metformin nano-structure to impede virulence of Staphylococcus aureus

Staphylococcus aureus is a prevalent etiological agent of health care associated and community acquired infections. Antibiotic abuse resulted in developing multidrug resistance in S. aureus that complicates treatment of infections. Targeting bacterial virulence using FDA approved medication offers an alternative to the antibiotics with no stress on bacterial viability. Using nanomaterials as anti-virulence agent against S. aureus virulence factors is a valuable approach. This study aims to investigate the impact of metformin (MET), metformin nano (MET-Nano), silver metformin nano structure (Ag-MET-Ns) and silver nanoparticles (AgNPs) on S. aureus virulence and pathogenicity. The in vitro results showed a higher inhibitory activity against S. aureus virulence factors with both MET-Nano and Ag-MET-Ns treatment. However, genotypically, it was found that except for agrA and icaR genes that are upregulated, the tested agents significantly downregulated the expression of crtM, sigB, sarA and fnbA genes, with Ag-MET-Ns being the most efficient one. MET-Nano exhibited the highest protection against S. aureus infection in mice. These data indicate the promising anti-virulence activity of nanoformulations especially Ag-MET-Ns against multidrug resistant S. aureus by inhibiting quorum sensing signaling system.