Combination Therapy with Phytochemical Based Quorum Sensing Inhibitor and Ciprofloxacin against Virulence of Pseudomonas aeruginosa

Pseudomonas aeruginosa, a nosocomial pathogen, establishes infection by the expression of an array of virulence factors and by formation of antibiotic resistant biofilms which are regulated by quorum sensing. Blocking quorum sensing of this pathogen is found to be an attractive approach for therapy. Natural products are known to have the potential to act as quorum sensing inhibitors. We screened constituents of garlic and cranberry for quorum sensing inhibition (QSI) property by bioassay guided fractionation using reporter strains E.coli MG4 and Agrobacterium tumefaciens A136. Further the QSI compounds were separated by TLC, column chromatography and characterized by HPLC, FTIR, NMR and MS. Then the QSIs were analysed in combination with ciprofloxacin for their effect on virulence factors (protease, elastase, rhamnolipid, alginate and pyochelin), motility, generation and eradication of biofilms of P.aeruginosa. Virulence factors, three forms of motility as well as biofilm formation got significantly (p<0.01) reduced with the combination of QSIs and ciprofloxacin compared to both these agents alone. There was also significant reduction (p<0.05) in preformed biofilms. Usage of herbal product- antibiotic combination was found to be promising against P.aeruginosa as the former makes the pathogen more susceptible to latters' effect.