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Biosensor for Detection of Antibiotic Resistant Staphylococcus Bacteria
Published on: May 8, 2013
A TAT Peptide-Functionalized Liposome Delivery Phage System (TAT-Lip@PHM) for an Enhanced Eradication of
Kaixin Liu1, Xin Lu2, Xudong Guo1
1Chinese PLA Center for Disease Control and Prevention, Beijing 100071, China.
Abstract:
Background: Intracellular bacteria frequently result in chronic and recurrent infections. MRSA is one of the most prevalent facultative intracellular bacteria in clinical infections. The drug resistance of MRSA and the difficulty of most antibiotics in entering cells result in a suboptimal clinical efficacy of antibiotics in the treatment of intracellular MRSA. Bacteriophages represent a promising alternative therapy in the context of the current antimicrobial resistance crisis. Nevertheless, the low efficiency of phage entry into cells and their rapid inactivation remain challenges in the treatment of intracellular MRSA using phages. The utilization of functionalized carriers for the delivery of phages into cells and their protection represents a feasible strategy. Methods: In this study, a new MRSA bacteriophage (vB_SauS_PHM) was isolated from hospital sewage, exhibiting the characteristics of short incubation period, large lytic amount, and good environmental tolerance. Subsequently, vB_SauS_PHM was encapsulated by TAT peptide-functionalized liposomes through microfluidic technology and size-exclusion chromatography (SEC), forming a phage delivery system, designated TAT-Lip@PHM. Results: The encapsulation rate of the phage by TAT-Lip@PHM was 20.3%, and the cell entry efficiency was ≥90% after 8 h. The 24 h eradication rate of 300 μg/mL TAT-Lip@PHM against intracellular MRSA was 94.05% (superior to the 21.24% and 44.90% of vB_SauS_PHM and Lip@PHM, respectively), while the mammalian cell activity was >85% after 24 h incubation. Conclusions: The TAT-Lip@PHM effectively delivered the phage into the cell and showed an excellent killing effect on intracellular MRSA with low cytotoxicity. This work provides a technical reference for the application of phages in the treatment of intracellular bacterial infection.
Insights
This study developed a novel phage delivery system, TAT-Lip@PHM, to combat intracellular MRSA infections. The system efficiently delivers bacteriophages into cells, achieving a 94.05% eradication rate with minimal toxicity, offering a promising alternative to antibiotics.
Area of Science:
- Microbiology
- Biotechnology
- Drug Delivery Systems
Background:
- Intracellular bacteria like Methicillin-resistant Staphylococcus aureus (MRSA) cause persistent infections.
- Antibiotic resistance and poor cellular penetration limit treatment efficacy against intracellular MRSA.
- Bacteriophages offer a potential alternative but face challenges in cellular delivery and stability.
Purpose of the Study:
- To develop and evaluate a novel bacteriophage-based delivery system for treating intracellular MRSA infections.
- To enhance phage efficacy and overcome limitations of traditional antibiotic therapies.
Main Methods:
- Isolation of a novel MRSA bacteriophage (vB_SauS_PHM).
- Encapsulation of the bacteriophage within TAT peptide-functionalized liposomes using microfluidics and SEC, creating TAT-Lip@PHM.
- Assessment of phage encapsulation rate, cellular uptake efficiency, intracellular MRSA eradication rate, and mammalian cell cytotoxicity.
Main Results:
- The TAT-Lip@PHM system demonstrated a 20.3% phage encapsulation rate and over 90% cell entry efficiency within 8 hours.
- A 24-hour treatment with 300 μg/mL TAT-Lip@PHM achieved a 94.05% eradication rate of intracellular MRSA.
- The system exhibited high mammalian cell viability (>85%) after 24 hours, indicating low cytotoxicity.
Conclusions:
- The TAT-Lip@PHM system effectively delivers bacteriophages into host cells.
- This novel system shows significant potential for treating intracellular MRSA infections with high efficacy and low toxicity.
- Provides a valuable technical framework for developing phage-based therapies against intracellular bacterial pathogens.
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