Investigating the mechanism of eradication of MDR bacteria by inorganic, organic, and protein-based nanoparticles (NPERDMDR)

The increase in nosocomial infections is adding a substantial burden to the medical system as they result in extended periods of hospitalization. This increase is strongly associated with the emergence of antimicrobial-resistant bacterial strains over the last two decades.The widespread use of antibiotics has resulted in the evolution and spread of these resistant genetic determinants: multidrug resistant (MDR) and extremely drug resistant (XDR) bacteria. There is an urgent need to develop novel antimicrobial agents to be able to kill antibiotic-resistant bacteria.

Completed project

Preliminary results show that inorganic mixed metal and that quorum sensing inhibiting enzyme (QSIE) NPs are effective in biofilm inhibition in pathogenic bacteria. We will investigate why these NPs are effective by studying clinical isolates of MDR bacteria in both planktonic and biofilm forms.

The proposed project brings together experts from Israel, Canada, and Spain. Gedanken will sonochemically synthesize and characterize MMO and ANB NPs. Tzanov will synthesize the QSIE NPs, study NP interactions with bacterial membrane models, and together with Banin will evaluate the efficacy of the of NPs against both planktonic and biofilm cultures. Bach will investigate the cytotoxicity and immunological response of the NPs in human cell lines and murine models infected with MDR bacteria, and develop a model of NP antibacterial mechanism using proteomics. Hafeli will perform pharmacokinetic analysis and NP distribution using bioimaging in murine models.

The significance of this project is to provide alternative antibacterial agents to tackle an emergent issue in our society.

 

Project partners

  • Aharon Gedanken, Bar-Ilan University, Israel (Coordinator)
  • Horacio Bach, University of British Columbia, Canada
  • Tzanko Tzanov, Universitat Politecnica de Catalunya, Spain
  • Ehud Barin, Bar-Ilan University, Israel
  • Urs Hafelli, University of British Columbia, Canada

 

Publications