Knocking down Pseudomonas aeruginosa virulence by oral hypoglycemic metformin nano emulsion.

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.