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Lung-Targeting Lysostaphin Microspheres for Methicillin-Resistant Staphylococcus aureus Pneumonia Treatment and
Xiuhui Lin1, Jian He2, Wanlin Li2
1Department of Infectious Diseases, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, China.
Abstract:
Multifunctional antimicrobial strategies are urgently needed to treat methicillin-resistant Staphylococcus aureus (MRSA) caused pneumonia due to its increasing resistance, enhanced virulence, and high pathogenicity. Here, we report that lysostaphin, a bacteriolytic enzyme, encapsulated within poly(lactic-co-glycolic acid) microspheres (LyIR@MS) specially treats planktonic MRSA bacteria, mature biofilms, and related pneumonia. Optimized LyIR@MS with suitable diameters could deliver a sufficient amount of lysostaphin to the lung without a decrease in survival rate after intravenous injection. Furthermore, the degradable properties of the carrier make it safe for targeted release of lysostaphin to eliminate MRSA, repressing the expression of virulence genes and improving the sensitivity of biofilms to host neutrophils. In the MRSA pneumonia mouse model, treatment or prophylaxis with LyIR@MS significantly improved survival rate and relieved inflammatory injury without introducing adverse events. These findings suggest the clinical translational potential of LyIR@MS for the treatment of MRSA-infected lung diseases.
Insights
New microsphere technology effectively treats MRSA pneumonia by delivering lysostaphin, a bacteriolytic enzyme. This approach combats drug-resistant bacteria, biofilms, and lung infections with improved safety and efficacy.
Area of Science:
- Biomedical Engineering
- Infectious Diseases
- Drug Delivery Systems
Background:
- Methicillin-resistant Staphylococcus aureus (MRSA) pneumonia poses a significant threat due to rising antibiotic resistance and high pathogenicity.
- Novel therapeutic strategies are crucial to combat MRSA infections effectively.
Purpose of the Study:
- To develop and evaluate multifunctional antimicrobial microspheres for treating MRSA-induced pneumonia.
- To assess the efficacy of lysostaphin-loaded poly(lactic-co-glycolic acid) microspheres (LyIR@MS) against planktonic MRSA, biofilms, and pneumonia models.
Main Methods:
- Encapsulation of lysostaphin into poly(lactic-co-glycolic acid) microspheres (LyIR@MS) with optimized diameters.
- Intravenous administration of LyIR@MS in a mouse model of MRSA pneumonia.
- Evaluation of therapeutic effects on bacterial load, virulence gene expression, biofilm sensitivity, survival rates, and inflammatory responses.
Main Results:
- Optimized LyIR@MS demonstrated safe intravenous delivery to the lungs, releasing sufficient lysostaphin.
- LyIR@MS effectively targeted planktonic MRSA, mature biofilms, and reduced MRSA pneumonia severity.
- Treatment significantly improved survival rates, alleviated lung inflammatory injury, and repressed MRSA virulence gene expression.
Conclusions:
- LyIR@MS represent a promising multifunctional antimicrobial strategy for treating MRSA-infected lung diseases.
- The biodegradable microsphere system offers targeted drug delivery and enhances the host immune response against MRSA.
- These findings highlight the clinical translational potential of LyIR@MS for combating challenging MRSA infections.
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