Enhanced antimicrobial, anti-biofilm, and efflux pump inhibitory effects of ursolic acid-conjugated magnetic nanoparticles against clinical isolates of multidrug-resistant Pseudomonas aeruginosa.

OBJECTIVES

In the present study, we investigate the effect of FeO nanoparticles conjugated with ursolic acid (FeONPs@UA) on inhibiting the growth, biofilm-forming ability and efflux pump activity in clinical isolates of Pseudomonas aeruginosa with multiple drug resistance.

METHODS

Iron oxide NPs conjugated with ursolic acid (FeONPs@UA) were synthesized. Physicochemical features of the NPs were studied by FT-IR, XRD, EDAX, and TEM. The antibacterial and antibiofilm effects of FeONPs@UA against P. aeruginosa isolates were determined by broth microdilution and microtiter plate methods, respectively. The efflux pump inhibitory effect of FeONPs@UA was determined using Cartwheel method and through determining the expression level of efflux pump genes, including mexA and oprD in selected P. aeruginosa isolates treated with sub-MIC concentration of FeONPs@UA by real-time PCR.

RESULTS

In investigating the antimicrobial effect of FeONPs@UA, the MIC of these nanoparticles varied between 0.19 and 0.78 mg/mL and in the study of the anti-biofilm effect of FeONPs@UA, it caused a 68-75 % decrease in biofilm formation compared to the control. Moreover, in the Cartwheel test, the anti-efflux effect of these nanoparticles was confirmed at 1/4-MIC concentrations, and the expression of mexA and oprD genes was reduced in bacteria treated with FeONPs@UA compared to the control.

CONCLUSION

According to the results, the use of FeONPs@UA can provide a basis for the development of new treatments against drug-resistant bacteria in P. aeruginosa. This substance can improve the concentration of antibiotics in bacterial cells and increase their effectiveness by inhibiting the efflux in P. aeruginosa isolates.