Photoimmuno-antimicrobial therapy for Staphylococcus aureus implant infection

PLoS One. 2024 Mar 8;19(3):e0300069. doi: 10.1371/journal.pone.0300069. eCollection 2024.

Abstract

Introduction: Implant infections caused by Staphylococcus aureus are responsible for high mortality and morbidity worldwide. Treatment of these infections can be difficult especially when bacterial biofilms are involved. In this study we investigate the potential of infrared photoimmunotherapy to eradicate staphylococcal infection in a mouse model.

Methods: A monoclonal antibody that targets Wall Teichoic Acid surface components of both S. aureus and its biofilm (4497-IgG1) was conjugated to a photosensitizer (IRDye700DX) and used as photoimmunotherapy in vitro and in vivo in mice with a subcutaneous implant pre-colonized with biofilm of Staphylococcus aureus. A dose of 400 μg and 200 μg of antibody-photosensitizer conjugate 4497-IgG-IRDye700DXwas administered intravenously to two groups of 5 mice. In addition, multiple control groups (vancomycin treated, unconjugated IRDye700DX and IRDye700DX conjugated to a non-specific antibody) were used to verify anti-microbial effects.

Results: In vitro results of 4497-IgG-IRDye700DX on pre-colonized (biofilm) implants showed significant (p<0.01) colony-forming units (CFU) reduction at a concentration of 5 μg of the antibody-photosensitizer conjugate. In vivo, treatment with 4497-IgG-IRDye700DX showed no significant CFU reduction at the implant infection. However, tissue around the implant did show a significant CFU reduction with 400 μg 4497-IgG-IRDye700DX compared to control groups (p = 0.037).

Conclusion: This study demonstrated the antimicrobial potential of photoimmunotherapy for selectively eliminating S. aureus in vivo. However, using a solid implant instead of a catheter could result in an increased bactericidal effect of 4497-IgG-IRDye700DX and administration locally around an implant (per operative) could become valuable applications in patients that are difficult to treat with conventional methods. We conclude that photoimmunotherapy could be a potential additional therapy in the treatment of implant related infections, but requires further improvement.

MeSH terms

  • Animals
  • Anti-Bacterial Agents / pharmacology
  • Anti-Bacterial Agents / therapeutic use
  • Biofilms
  • Humans
  • Immunoglobulin G / pharmacology
  • Mice
  • Photosensitizing Agents / pharmacology
  • Photosensitizing Agents / therapeutic use
  • Staphylococcal Infections* / drug therapy
  • Staphylococcal Infections* / microbiology
  • Staphylococcus aureus*

Substances

  • Photosensitizing Agents
  • Anti-Bacterial Agents
  • Immunoglobulin G

Grants and funding

This research was funded by Health Holland, financed by the Netherlands Organization for Scientific Research (NWO), Grant number LSHM17026. The funders had no role in the study design, data collection and analysis, the decision to publish or the preparation of the manuscript.