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Published on: January 1, 2016
Phage-liposome nanoconjugates for orthopedic biofilm eradication
Lei Wang1, Tamta Tkhilaishvili2, Zheng Jiang1
1Department of Orthopedics, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, 200233 Shanghai, China.
Abstract:
Infection by multidrug-resistant (MDR) bacteria has become one of the biggest threats to public health worldwide. One reason for the difficulty in treatment is the lack of proper delivery strategies into MDR bacterial biofilms, where the thick extracellular polymeric substance (EPS) layer impedes the penetration of antibiotics and nanoparticles. Here, we propose a novel bioactive nanoconjugate of drug-loaded liposomes and bacteriophages for targeted eradication of the MDR biofilms in orthopedic infections. Phage Sb-1, which has the ability to degrade EPS, was conjugated with antibiotic-loaded liposomes. Upon encountering the biofilm, phage Sb-1 degrades the EPS structure, thereby increasing the sensitivity of bacteria to antibiotics and allowing the antibiotics to penetrate deeply into the biofilm. As a result, effective removal of MDR bacterial biofilm was achieved with low dose of antibiotics, which was proved in this study by both in vitro and in vivo investigations. Notably, in the rat prosthetic joint infection (PJI) model, we found that the liposome-phage nanoconjugates could effectively decrease the bacterial load in the infected area and significantly promote osteomyelitis recovery. It is therefore believed that the conjugation of bacteriophage and liposomes could open new possibilities for the treatment of orthopedic infections, possibly other infections in the deep tissues.
Insights
This study introduces a novel nanoconjugate combining antibiotic-loaded liposomes and bacteriophages to effectively treat multidrug-resistant bacterial biofilms in orthopedic infections, significantly reducing bacterial load and promoting recovery.
Area of Science:
- Biotechnology
- Infectious Diseases
- Nanomedicine
Background:
- Multidrug-resistant (MDR) bacterial infections pose a global health threat.
- Bacterial biofilms, particularly in orthopedic infections, are difficult to treat due to their protective extracellular polymeric substance (EPS) layer.
- Current antibiotic delivery methods struggle to penetrate these biofilms effectively.
Purpose of the Study:
- To develop a novel nanoconjugate for targeted eradication of MDR bacterial biofilms in orthopedic infections.
- To enhance antibiotic penetration and efficacy against biofilms using bacteriophage-mediated EPS degradation.
- To evaluate the in vitro and in vivo effectiveness of the nanoconjugate in treating prosthetic joint infections.
Main Methods:
- Conjugation of antibiotic-loaded liposomes with bacteriophage Sb-1, known for EPS degradation capabilities.
- In vitro assessment of nanoconjugate efficacy in degrading biofilms and increasing antibiotic sensitivity.
- In vivo evaluation using a rat prosthetic joint infection (PJI) model to assess bacterial load reduction and osteomyelitis recovery.
Main Results:
- The liposome-phage nanoconjugate successfully degraded the EPS layer of MDR biofilms.
- Significantly enhanced antibiotic penetration and efficacy were observed, allowing effective biofilm removal with a low antibiotic dose.
- In vivo studies demonstrated a substantial decrease in bacterial load and significant promotion of osteomyelitis recovery in the PJI model.
Conclusions:
- The developed bacteriophage-liposome nanoconjugate offers a promising strategy for treating MDR bacterial biofilms in orthopedic infections.
- This approach enhances antibiotic delivery and efficacy, potentially reducing treatment dosage and improving patient outcomes.
- The conjugation strategy holds potential for treating deep-tissue infections beyond orthopedic applications.
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