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Combating multidrug-resistant Gram-negative bacteria with structurally nanoengineered antimicrobial peptide polymers

Shu J Lam1, Neil M O'Brien-Simpson2, Namfon Pantarat2

  • 1Polymer Science Group, Department of Chemical &Biomolecular Engineering, The University of Melbourne, Parkville, Victoria 3010, Australia.

Nature Microbiology
|September 13, 2016
PubMed

Insights

New synthetic polymers called structurally nanoengineered antimicrobial peptide polymers (SNAPPs) show potent activity against drug-resistant Gram-negative bacteria, including

Area of Science:

  • Biochemistry
  • Materials Science
  • Infectious Diseases

Background:

  • Multidrug-resistant (MDR) Gram-negative bacteria pose a critical global health threat.
  • Existing treatments are limited by lack of efficacy and biocompatibility.

Purpose of the Study:

  • To evaluate the efficacy and toxicity of structurally nanoengineered antimicrobial peptide polymers (SNAPPs).
  • To investigate SNAPPs as a potential therapeutic for infections caused by MDR Gram-negative pathogens.

Main Methods:

  • Synthesized and characterized SNAPPs.
  • Tested SNAPPs against a panel of Gram-negative bacteria, including ESKAPE and colistin-resistant MDR (CMDR) strains.
  • Evaluated SNAPPs in vivo using a CMDR *Acinetobacter baumannii* infection model.
  • Assessed bacterial resistance development to SNAPPs.
  • Utilized microscopy and bioassays to elucidate the antimicrobial mechanism of SNAPPs.

Main Results:

  • SNAPPs demonstrated sub-micromolar activity against all tested Gram-negative bacteria, including CMDR strains.
  • SNAPPs showed low toxicity to host cells.
  • SNAPPs were effective in treating CMDR *Acinetobacter baumannii* infections in vivo.
  • No resistance to SNAPPs was observed in *A. baumannii*.
  • SNAPPs induce bacterial cell death via outer membrane destabilization, ion dysregulation, and apoptosis-like pathways.

Conclusions:

  • SNAPPs represent a promising new class of synthetic antimicrobial agents.
  • SNAPPs exhibit broad-spectrum efficacy against challenging MDR Gram-negative pathogens.
  • The multimodal mechanism of action may prevent resistance development, offering a potential solution to the antimicrobial resistance crisis.

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