Copper nanoparticles as an efflux pump inhibitor to tackle drug resistant bacteria

Abstract

We explored whether copper nanoparticles (CuNPs) can function as an efflux pump inhibitor and as an anti-biofilm agent. Our results showed that at 0.5× (0.065 mM) Minimum Inhibitory Concentration (MIC), CuNPs exhibited remarkable efflux inhibitory effect in wild type strains of both Staphylococcus aureus and Pseudomonas aeruginosa and less but significant efflux inhibitory effect against MRSA and drug resistant mutant strains of Staphylococcus aureus. At 1× MIC (0.13 mM) concentration, they significantly inhibited monoculture biofilms formed by Staphylococcus aureus and Pseudomonas aeruginosa. Membrane permeability, membrane integrity and confocal imaging provided insight into the mechanism of the antibacterial effect of CuNPs. Efflux inhibition and antibacterial effect of CuNPs was partly mediated by particle effect and partly by ion effect. A novel efflux pump inhibitory role for CuNPs is reported in our study. Proof of concept experiments revealed that CuNPs could reverse the MIC of the mutant Staphylococci aureus strain for ciprofloxacin by 4 fold (from 64 μg ml⁻¹ to 16 μg ml⁻¹), hence our study reveals that CuNPs could be potentially employed as bacterial adjuvants to curtail Multi Drug Resistant (MDR) bacteria.