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Targeting internalized Staphylococcus aureus using vancomycin-loaded nanoparticles to treat recurrent bloodstream infections

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journal contribution
posted on 27.07.2021, 16:47 by Danielle NaderDanielle Nader, Fajer Yousef, Nicola Kavanagh, Benedict RyanBenedict Ryan, Steven KerriganSteven Kerrigan
The bacterial pathogen Staphylococcus aureus is a leading cause of bloodstream infections, where patients often suffer from relapse despite antibiotic therapy. Traditional anti-staphylococcal drugs display reduced effectivity against internalised bacteria, but nanoparticles conjugated with antibiotics can overcome these challenges. In the present study, we aimed to characterise the internalisation and re-emergence of S. aureus from human endothelial cells and construct a new formulation of nanoparticles that target intracellular bacteria. Using an in vitro infection model, we demonstrated that S. aureus invades and persists within endothelial cells, mediated through bacterial extracellular surface adhesion, Fibronectin-binding protein A/B. After internalising, S. aureus localises to vacuoles as determined by transmission electron microscopy. Viable S. aureus emerges from endothelial cells after 48 h, supporting the notion that intracellular persistence contributes to infection relapses during bloodstream infections. Poly lactic-co-glycolic acid nanoparticles were formulated using a water-in-oil double emulsion method, which loaded 10% vancomycin HCl with 82.85% ± 12 encapsulation efficiency. These non-toxic nanoparticles were successfully taken up by cells and demonstrated a biphasic controlled release of 91 ± 4% vancomycin. They significantly reduced S. aureus intracellular growth within infected endothelial cells, which suggests future potential applications for targeting internalised bacteria and reducing mortality associated with bacteraemia.

Funding

Science Foundation Ireland (SFI) under Grant Number 13/CDA/2119

HEA/PRTLI Cycle 5 (BioAT—BioAnalysis and Therapeutics)

History

Comments

The original article is available at https://www.mdpi.com

Published Citation

Nader D, Yousef F, Kavanagh N, Ryan BK, Kerrigan SW. Targeting internalized Staphylococcus aureus using vancomycin-loaded nanoparticles to treat recurrent bloodstream infections. Antibiotics (Basel). 2021;10(5):581.

Publication Date

14 May 2021

PubMed ID

34068975

Department/Unit

  • School of Pharmacy and Biomolecular Sciences

Research Area

  • Vascular Biology
  • Immunity, Infection and Inflammation
  • Endocrinology
  • Biomaterials and Regenerative Medicine
  • Neurological and Psychiatric Disorders
  • Population Health and Health Services

Publisher

MDPI AG

Version

  • Published Version (Version of Record)