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Updated: Jul 31, 2025
Author Spotlight: Advancing Research on Candida albicans Biofilm-Associated Prosthetic Joint Infections
Published on: February 2, 2024
Protective effect of additional cathelicidin antimicrobial peptide PR-39 on prosthetic-joint infections
Yongjun Zhu1,2, Xuan Weng3, Jian Zhang4
1Department of Orthopedics, The Ninth People's Hospital of Chongqing, Chongqing, China.
Background:
Prosthetic-joint infection (PJI) is one of the severest complications after arthroplasty. However, antibiotics are not effective in the bacteria in biofilm outside the prosthetic-joint. Antimicrobial peptides have an efficient antimicrobial activity in staphylococcus aureus compared with conventional antibiotics.
Methods:
Bone marrow stem cells (BMSCs) were isolated, cultured and transfected with cathelicidins antimicrobial peptides proline-arginine-rich 39 amino acid peptide (PR-39) lentivirus. The expression of PR-39 gene in BMSCs was detected by RT-PCR, and the antibacterial activity of PR-39 was measured by agar diffusion method. The transfection efficiency was detected by fluorescence microscopy. The infection model of artificial knee joint in rabbits were established. Kirschner wire was used as the knee joint implant to implant the distal femur through the femoral intercondylar fossa of rabbits. 24 rabbits were randomly divided into 2 groups for the above operations: group A was inoculated 0.5 mL into the joint cavity immediately after the incision was sutured 1 × 107 Staphylococcus aureus of colony forming unit (CFU), group B was inoculated with Staphylococcus aureus and PR-39. After operation, the wound conditions and histological changes were observed by X-ray and optical microscope respectively, CRP and erythrocyte sedimentation rate were measured by test assay.
Results:
The transfection efficiency of lentivirus vectortransfected BMSCs was 74.09%. The supernatant of lentivirus vector had obvious inhibitory effect on Staphylococcus aureus, and the antibacterial rate was 98.43%. 100% infection observed in group A while few infection observed in group B; serum CRP and ESR at a high level in group A while decreased in group B after operation. There were no significant difference in CRP and ESR between the pLV/PR-39 group and pLV/EGFP group at day 1 and 3 respectively after surgery. However, CRP and ESR in the pLV/PR-39 groupwere significantly lower than the pLV/EGFP group at day 7 and 14 respectively after operation.
Conclusions:
Rabbits planted BMSCs expressing PR-39 were significantly increased resistance to Staphylococcus aureus in PJI than control group thus showing great potential for preventing implant-associated infection. It will provide a potential new therapeutic agent for implant-associated infection.
Insights
Bone marrow stem cells engineered with antimicrobial peptides show promise in preventing prosthetic-joint infections caused by Staphylococcus aureus. This approach offers a potential new therapy for implant-associated infections.
Area of Science:
- Biomedical Engineering
- Infectious Diseases
- Regenerative Medicine
Background:
- Prosthetic-joint infection (PJI) is a severe complication of arthroplasty, often resistant to conventional antibiotics due to bacterial biofilm formation.
- Antimicrobial peptides (AMPs) demonstrate potent activity against bacteria like Staphylococcus aureus, surpassing traditional antibiotics.
Purpose of the Study:
- To investigate the efficacy of bone marrow stem cells (BMSCs) genetically modified to express the antimicrobial peptide PR-39 for preventing Staphylococcus aureus-induced PJI.
- To evaluate the therapeutic potential of PR-39-expressing BMSCs in a rabbit knee joint infection model.
Main Methods:
- BMSCs were isolated, cultured, and transfected with a lentivirus vector encoding the PR-39 peptide.
- Antibacterial activity of PR-39 was assessed using the agar diffusion method, and transfection efficiency was confirmed via fluorescence microscopy.
- A rabbit knee PJI model was established by intra-articular inoculation of Staphylococcus aureus; rabbits received either PR-39-expressing BMSCs or control BMSCs.
Main Results:
- Transfection efficiency of BMSCs with the PR-39 lentivirus vector reached 74.09%.
- PR-39 demonstrated significant antibacterial activity against Staphylococcus aureus (98.43% inhibition rate).
- Rabbits treated with PR-39-expressing BMSCs showed significantly reduced infection rates and lower serum C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) levels compared to controls at later time points (7 and 14 days post-surgery).
Conclusions:
- BMSCs engineered to express PR-39 significantly enhance resistance to Staphylococcus aureus in a PJI model.
- This strategy holds considerable potential for preventing implant-associated infections.
- PR-39-expressing BMSCs represent a promising novel therapeutic agent for managing implant-associated infections.
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