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Updated: Feb 1, 2026

Development and Assessment of Intracellular Infection Models for Staphylococcus aureus
Published on: January 17, 2025
Exosome-encapsulated antibiotic against intracellular infections of methicillin-resistant Staphylococcus aureus
Xiaohong Yang1, Gongming Shi1, Jian Guo1
1Chongqing Key Laboratory of Natural Product Synthesis and Drug Research, School of Pharmaceutical Sciences, Chongqing University, Chongqing 401331, People's Republic of China, wangchenhui@cqu.edu.cn; yun.he@cqu.edu.cn.
Background:
Staphylococcus aureus survival inside phagocytes is considered to provide a reservoir of bacteria that are relatively protected from antibiotics, thus enabling long-term colonization of the host and explaining clinical failures and relapses after antibiotic therapy.
Purpose:
The objective of this study was to develop a nanovesicle using exosomes loaded with linezolid to overcome intracellular infections by pathogenic bacteria.
Methods:
Exosomes were collected from the culture supernatants of RAW 264.7 cells. Their size distribution and zeta potential were characterized by dynamic light scattering, their morphology was characterized by transmission electron microscopy, and their protein content (CD63 and Flotillin 1) was assessed by Western blotting. Linezolid was incorporated into exosomes by co-incubation at 37°C and it's accumulation in RAW264.7 cells and release in vitro were determined by high performance liquid chromatography. The intracellular bactericidal effect was evaluated in methicillin-resistant S. aureus (MRSA)-infected macrophages in vitro and MRSA peritonitis model in vivo.
Results:
We prepared a nanoformulation of the antibiotic linezolid using exosomes harvested from mouse RAW264.7 macrophages. The exosomal formulation of linezolid was more effective against intracellular MRSA infections in vitro and in vivo than the free linezolid. Our data also showed no signs of cytotoxicity in macrophages.
Conclusion:
Exosomes provide an effective alternative for intracellular antibiotic delivery of antibiotic that is efficacious, cost-effective, and safe. This regimen can be viewed as a potential antimicrobial agent for use against intracellular infections.
Insights
Exosomes loaded with linezolid effectively target intracellular Staphylococcus aureus infections. This exosome-based antibiotic delivery system shows promise for treating persistent bacterial infections and preventing relapse.
Area of Science:
- Nanotechnology
- Drug Delivery
- Microbiology
Background:
- Staphylococcus aureus survives within host phagocytes, creating antibiotic-protected reservoirs.
- This intracellular survival leads to persistent infections, treatment failures, and relapses.
Purpose of the Study:
- To develop an exosome-based nanovesicle for delivering the antibiotic linezolid.
- To overcome intracellular infections caused by pathogenic bacteria, specifically targeting Staphylococcus aureus.
Main Methods:
- Exosomes were isolated from RAW 264.7 macrophage cell culture supernatants.
- Linezolid was loaded into exosomes, and its efficacy was tested against methicillin-resistant S. aureus (MRSA) in vitro and in vivo.
- Characterization included dynamic light scattering, transmission electron microscopy, and Western blotting for protein content.
Main Results:
- Exosomes effectively encapsulated linezolid, forming a nanoformulation.
- The exosomal linezolid formulation demonstrated superior efficacy against intracellular MRSA compared to free linezolid.
- No cytotoxicity was observed in macrophages treated with the exosomal formulation.
Conclusions:
- Exosomes serve as a safe, cost-effective, and efficacious platform for intracellular antibiotic delivery.
- This exosome-based approach represents a potential antimicrobial strategy for intracellular bacterial infections.
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