Oxidative stress, DNA, and membranes targets as modes of antibacterial and antibiofilm activity of facile synthesized biocompatible keratin-copper nanoparticles against multidrug resistant uro-pathogens

World J Microbiol Biotechnol. 2022 Jan 6;38(2):20. doi: 10.1007/s11274-021-03187-z.

Abstract

Escherichia coli and Enterococcus faecalis are two of the most prevalent uro-pathogens and are difficult to treat as they acquire multidrug-resistant traits. In this study, the main objective was to develop biocompatible copper nanoparticles using chicken feather keratin protein (CuNPs-K) and to investigate their impact on multidrug-resistant (MDR) uro-pathogens, E. coli and E. faecalis, under both single and mixed culture conditions. CuNPs-K were characterised by UV-Vis spectroscopy, dynamic light scattering, X-ray diffraction, Fourier transform infrared spectroscopy, and docking experiments. The MIC values of CuNPs-K against single and mixed planktonic cultures were 50 μg/ml and 75 μg/ml, respectively. CuNPs-K efficiently disrupted the biofilm of single and mixed uro-pathogen cultures by eliminating sessile cells. This biofilm disruption may be attributed to a decline in the production of extracellular polymeric substances in both single and mixed bacterial cultures treated with CuNPs-K. Moreover, selective antimicrobial activity was determined by selectivity assays using T24 cells. CuNPs-K targets both the bacterial membrane and DNA with elevated reactive oxygen species (ROS) as their bactericidal mode of action. This comprehensive antimicrobial activity of CuNPs-K was further confirmed in vivo by using the zebra fish model. In this study, CuNPs-K effectively reduced bacterial load with increased survivability of infected zebrafish. All these results suggest that CuNPs-K can be explored as an exceptional antibacterial agent against MDR uro-pathogenic E. coli and E. faecalis.

Keywords: DNA binding; Keratin-copper-nanoparticles; Multidrug-resistance-uro-pathogens; Reactive oxygen species; Selective-antibacterial properties; Zebrafish model.

MeSH terms

  • Animals
  • Anti-Bacterial Agents / pharmacology*
  • Biofilms / drug effects
  • Cell Membrane / drug effects*
  • Copper / chemistry
  • Copper / pharmacology*
  • DNA / drug effects*
  • Disease Models, Animal
  • Drug Resistance, Multiple, Bacterial / drug effects*
  • Escherichia coli / drug effects
  • Escherichia coli Infections
  • Keratins / chemistry
  • Keratins / pharmacology*
  • Metal Nanoparticles / chemistry*
  • Microbial Sensitivity Tests
  • Oxidative Stress / drug effects*
  • Reactive Oxygen Species
  • Spectroscopy, Fourier Transform Infrared
  • X-Ray Diffraction
  • Zebrafish

Substances

  • Anti-Bacterial Agents
  • Reactive Oxygen Species
  • Keratins
  • Copper
  • DNA