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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.

Long-term antibiotic treatment results in the spread of multi-drug resistance in Pseudomonas aeruginosa that complicates treatment. Anti-virulence agents can be viewed as alternative options that cripple virulence factors of the bacteria to facilitate their elimination by the host immunity. The use of nanoparticles in the inhibition of P. aeruginosa virulence factors is a promising strategy. This study aims to study the effect of metformin (MET), metformin nano emulsions (MET-NEs), silver metformin nano emulsions (Ag-MET-NEs) and silver nanoparticles (AgNPs) on P. aeruginosa virulence factors’ expression. The phenotypic results showed that MET-NEs had the highest virulence inhibitory activity. However, concerning RT-PCR results, all tested agents significantly decreased the expression of quorum sensing regulatory genes of P. aeruginosa; lasR, lasI, pqsA, fliC, exoS and pslA, with Ag-MET-NEs being the most potent one, however, it failed to protect mice from P. aeruginosa pathogenesis. MET-NEs showed the highest protective activity against pseudomonal infection in vivo. Our findings support the promising use of nano formulations particularly Ag-MET-NEs as an alternative against multidrug resistant pseudomonal infections via inhibition of virulence factors and quorum sensing gene expression.

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