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Updated: Feb 5, 2026
Author Spotlight: Advancing Research on Candida albicans Biofilm-Associated Prosthetic Joint Infections
Published on: February 2, 2024
Mouse model of Gram-negative prosthetic joint infection reveals therapeutic targets
John M Thompson1, Robert J Miller2, Alyssa G Ashbaugh2
1Department of Orthopaedic Surgery.
Abstract:
Bacterial biofilm infections of implantable medical devices decrease the effectiveness of antibiotics, creating difficult-to-treat chronic infections. Prosthetic joint infections (PJI) are particularly problematic because they require prolonged antibiotic courses and reoperations to remove and replace the infected prostheses. Current models to study PJI focus on Gram-positive bacteria, but Gram-negative PJI (GN-PJI) are increasingly common and are often more difficult to treat, with worse clinical outcomes. Herein, we sought to develop a mouse model of GN-PJI to investigate the pathogenesis of these infections and identify potential therapeutic targets. An orthopedic-grade titanium implant was surgically placed in the femurs of mice, followed by infection of the knee joint with Pseudomonas aeruginosa or Escherichia coli. We found that in vitro biofilm-producing activity was associated with the development of an in vivo orthopedic implant infection characterized by bacterial infection of the bone/joint tissue, biofilm formation on the implants, reactive bone changes, and inflammatory immune cell infiltrates. In addition, a bispecific antibody targeting P. aeruginosa virulence factors (PcrV and Psl exopolysaccharide) reduced the bacterial burden in vivo. Taken together, our findings provide a preclinical model of GN-PJI and suggest the therapeutic potential of targeting biofilm-associated antigens.
Insights
This study developed a mouse model for Gram-negative prosthetic joint infections (GN-PJI). A new antibody treatment targeting bacterial biofilms showed promise in reducing infection burden, offering hope for chronic implant infections.
Area of Science:
- Biomedical Engineering
- Infectious Diseases
- Orthopedic Surgery
Background:
- Bacterial biofilm infections on medical implants cause chronic, hard-to-treat conditions like prosthetic joint infections (PJI).
- Gram-negative PJI (GN-PJI) are rising and associated with poorer outcomes compared to Gram-positive PJI.
- Existing PJI models primarily focus on Gram-positive bacteria, limiting research into GN-PJI.
Purpose of the Study:
- To establish a preclinical mouse model for Gram-negative prosthetic joint infections (GN-PJI).
- To investigate the pathogenesis of GN-PJI.
- To identify potential therapeutic targets for GN-PJI.
Main Methods:
- Surgically implanted orthopedic-grade titanium implants in mouse femurs.
- Infected knee joints with Gram-negative bacteria: Pseudomonas aeruginosa and Escherichia coli.
- Evaluated biofilm formation, bone/joint tissue infection, bone changes, and immune response.
Main Results:
- Developed a GN-PJI model characterized by biofilm formation on implants and bone/joint infection.
- Demonstrated a correlation between in vitro biofilm production and in vivo infection severity.
- A bispecific antibody targeting P. aeruginosa virulence factors (PcrV, Psl) significantly reduced bacterial burden.
Conclusions:
- The developed mouse model effectively replicates key features of GN-PJI.
- Targeting biofilm-associated antigens, such as PcrV and Psl, shows therapeutic potential for GN-PJI.
- This model serves as a valuable tool for future GN-PJI research and therapeutic development.
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