Vancomycin-Loaded Isogenous Membrane Vesicles for Macrophage Activation and Intracellular Methicillin-Resistant...

Area of Science:

• Nanomedicine
• Microbiology
• Infectious Diseases

Background:

• Methicillin-resistant Staphylococcus aureus (MRSA) is a multidrug-resistant pathogen that persists within macrophages, causing difficult-to-treat infections.
• Conventional antibiotics struggle to penetrate host cells, limiting their effectiveness against intracellular MRSA.

Purpose of the Study:

• To develop and evaluate vancomycin-loaded nanoparticles derived from bacterial membrane vesicles for enhanced intracellular MRSA clearance.
• To assess the safety and efficacy of this novel nanotherapeutic approach in vitro and in vivo.

Main Methods:

• Vancomycin (VAN) was encapsulated into membrane vesicles (ΔagrA MVs) from an attenuated Staphylococcus aureus strain, creating VAN-loaded nanoparticles (ΔagrA MV-VAN).
• In vitro studies assessed nanoparticle drug release, MRSA eradication, macrophage uptake, and M1 polarization.
• In vivo experiments evaluated the safety and efficacy of ΔagrA MV-VAN in treating abdominal MRSA infections in animal models.

Main Results:

• ΔagrA MV-VAN exhibited sustained vancomycin release and effectively eradicated extracellular MRSA.
• Macrophages actively internalized ΔagrA MV-VAN, leading to intracellular vancomycin accumulation and M1 polarization, enhancing MRSA killing.
• In vivo studies demonstrated that ΔagrA MV-VAN is safe and effectively clears intracellular MRSA in abdominal infections.

Conclusions:

• Bacterial-derived vesicles serve as effective carriers for targeted antibiotic delivery to intracellular pathogens.
• This nanotherapeutic strategy overcomes limitations of conventional antibiotics against intracellular multidrug-resistant pathogens like MRSA.