Delivery of antibacterial silver nanoclusters to Pseudomonas aeruginosa using species-specific DNA aptamers

J Med Microbiol. 2020 Apr;69(4):640-652. doi: 10.1099/jmm.0.001174.

Abstract

Introduction. The use of silver as an antimicrobial therapeutic is limited by its toxicity to host cells compared with that required to kill bacterial pathogens.Aim. To use aptamer targeting of DNA scaffolded silver nanoclusters as an antimicrobial agent for treating Pseudomonas aeruginosa infections.Methodology. Antimicrobial activity was assessed in planktonic cultures and in vivo using an invertebrate model of infection.Results. The aptamer conjugates that we call aptabiotics have potent antimicrobial activity. Targeted silver nanoclusters were more effective at killing P. aeruginosa than the equivalent quantity of untargeted silver nanoclusters. The aptabiotics have an IC50 of 1.3-2.6 µM against planktonically grown bacteria. Propidium iodide staining showed that they rapidly depolarize bacterial cells to kill approximately 50 % of the population within 10 min following treatment. In vivo testing in the Galleria mellonella model of infection prolonged survival from an otherwise lethal infection.Conclusion. Using P. aeruginosa as a model, we show that targeting of DNA-scaffolded silver nanoclusters with an aptamer has effective fast-acting antimicrobial activity in vitro and in an in vivo animal model.

Keywords: Pseudomonas aeruginosa; antibacterial; aptamers; nanoclusters; silver.

MeSH terms

  • Animals
  • Anti-Bacterial Agents / chemistry
  • Anti-Bacterial Agents / pharmacology*
  • Aptamers, Nucleotide / chemistry*
  • Aptamers, Nucleotide / genetics
  • Humans
  • Microbial Sensitivity Tests
  • Moths
  • Nanostructures / chemistry*
  • Pseudomonas Infections / drug therapy*
  • Pseudomonas Infections / microbiology
  • Pseudomonas aeruginosa / drug effects*
  • Pseudomonas aeruginosa / genetics
  • Pseudomonas aeruginosa / metabolism
  • Silver / chemistry
  • Silver / pharmacology*

Substances

  • Anti-Bacterial Agents
  • Aptamers, Nucleotide
  • Silver