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Nanomechanics of Drug-target Interactions and Antibacterial Resistance Detection
Published on: October 25, 2013
Targeting Internalized Staphylococcus aureus Using Vancomycin-Loaded Nanoparticles to Treat Recurrent Bloodstream
Danielle Nader1, Fajer Yousef1, Nicola Kavanagh1
1Cardiovascular Infection Research Group, School of Pharmacy and Biomolecular Sciences, RCSI University of Medicine and Health Sciences, 123 St. Stephens Green, Dublin 2, Ireland.
Abstract:
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.
Insights
Staphylococcus aureus causes bloodstream infections and relapses by hiding inside endothelial cells. New nanoparticles effectively target and reduce these intracellular bacteria, offering hope for treating persistent infections.
Area of Science:
- Microbiology
- Nanotechnology
- Infectious Diseases
Background:
- Staphylococcus aureus is a major cause of bloodstream infections.
- Intracellular bacteria are difficult to treat with conventional antibiotics, leading to infection relapse.
- Targeting intracellular pathogens is crucial for improving treatment outcomes.
Purpose of the Study:
- To characterize Staphylococcus aureus internalisation and re-emergence from human endothelial cells.
- To develop novel nanoparticles for targeting intracellular bacteria.
- To evaluate the efficacy of vancomycin-loaded nanoparticles against intracellular S. aureus.
Main Methods:
- In vitro infection model using human endothelial cells.
- Transmission electron microscopy to determine bacterial localization.
- Formulation and characterization of poly lactic-co-glycolic acid nanoparticles loaded with vancomycin HCl.
- Assessment of nanoparticle uptake, drug release, and antibacterial activity.
Main Results:
- Staphylococcus aureus invades and persists within endothelial cells, mediated by Fibronectin-binding protein A/B.
- Internalized bacteria are found within vacuoles and re-emerge after 48 hours.
- Vancomycin-loaded nanoparticles showed high encapsulation efficiency and controlled release.
- Nanoparticles significantly reduced intracellular S. aureus growth and were non-toxic.
Conclusions:
- Intracellular persistence of S. aureus in endothelial cells contributes to infection relapse.
- Developed nanoparticles are effective in targeting and reducing intracellular S. aureus.
- This nanotechnology approach holds potential for treating bacteraemia and reducing mortality.
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