Biomolecule-corona formation confers resistance of bacteria to nanoparticle-induced killing: Implications for the design of improved nanoantibiotics

Svenja Siemer, Dana Westmeier, Matthias Barz, Jonas Eckrich, Désirée Wünsch, Christof Seckert, Christian Thyssen, Oliver Schilling, Mike Hasenberg, Chengfan Pang, Dominic Docter, Shirley K Knauer, Roland H Stauber, Sebastian Strieth*

*Corresponding author for this work

Research output: Contribution to journalJournal articleResearchpeer-review

Abstract

Multidrug-resistant bacterial infections are a global health threat. Nanoparticles are thus investigated as novel antibacterial agents for clinical practice, including wound dressings and implants. We report that nanoparticles' bactericidal activity strongly depends on their physical binding to pathogens, including multidrug-resistant primary clinical isolates, such as Staphylococcus aureus, Klebsiella pneumoniae or Enterococcus faecalis. Using controllable nanoparticle models, we found that nanoparticle-pathogen complex formation was enhanced by small nanoparticle size rather than material or charge, and was prevented by 'stealth' modifications. Nanoparticles seem to preferentially bind to Gram-positive pathogens, such as Listeria monocytogenes, S. aureus or Streptococcus pyrogenes, correlating with enhanced antibacterial activity. Bacterial resistance to metal-based nanoparticles was mediated by biomolecule coronas acquired in pathophysiological environments, such as wounds, the lung, or the blood system. Biomolecule corona formation reduced nanoparticles' binding to pathogens, but did not impact nanoparticle dissolution. Our results provide a mechanistic explanation why nano-sized antibiotics may show reduced activity in clinically relevant environments, and may inspire future nanoantibiotic designs with improved and potentially pathogen-specific activity.

Original languageEnglish
JournalBiomaterials
Volume192
Pages (from-to)551-559
ISSN0142-9612
DOIs
Publication statusPublished - 2019

Keywords

  • Antibiotic nanomaterials
  • Bacteria
  • Biocorona
  • Implants
  • MRSA
  • Multidrug-resistant pathogens
  • Nanomedicine
  • Nanoparticles
  • Resistance

Cite this

Siemer, S., Westmeier, D., Barz, M., Eckrich, J., Wünsch, D., Seckert, C., Thyssen, C., Schilling, O., Hasenberg, M., Pang, C., Docter, D., Knauer, S. K., Stauber, R. H., & Strieth, S. (2019). Biomolecule-corona formation confers resistance of bacteria to nanoparticle-induced killing: Implications for the design of improved nanoantibiotics. Biomaterials, 192, 551-559. https://doi.org/10.1016/j.biomaterials.2018.11.028