Photoimmuno-antimicrobial therapy for Staphylococcus aureus implant infection.

Autor: Dijk BV; Department of Orthopedics, University Medical Center Utrecht, Utrecht, The Netherlands., Oliveira S; Department of Pharmaceutical Sciences, Faculty of Science, Utrecht University, Utrecht, The Netherlands.; Department of Biology, Faculty of Science, Utrecht University, Utrecht, The Netherlands., Hooning van Duyvenbode JFF; Department of Orthopedics, University Medical Center Utrecht, Utrecht, The Netherlands., Nurmohamed FRHA; Department of Orthopedics, University Medical Center Utrecht, Utrecht, The Netherlands., Mashayekhi V; Department of Biology, Faculty of Science, Utrecht University, Utrecht, The Netherlands., Hernández IB; Department of Pharmaceutical Sciences, Faculty of Science, Utrecht University, Utrecht, The Netherlands., van Strijp J; Department of Medical Microbiology, University Medical Centre Utrecht, Utrecht, The Netherlands., de Vor L; Department of Medical Microbiology, University Medical Centre Utrecht, Utrecht, The Netherlands., Aerts PC; Department of Medical Microbiology, University Medical Centre Utrecht, Utrecht, The Netherlands., Vogely HC; Department of Orthopedics, University Medical Center Utrecht, Utrecht, The Netherlands., Weinans H; Department of Orthopedics, University Medical Center Utrecht, Utrecht, The Netherlands.; Department of Biomechanical Engineering, Delft University of Technology, Delft, The Netherlands., van der Wal BCH; Department of Orthopedics, University Medical Center Utrecht, Utrecht, The Netherlands.
Jazyk: angličtina
Zdroj: PloS one [PLoS One] 2024 Mar 08; Vol. 19 (3), pp. e0300069. Date of Electronic Publication: 2024 Mar 08 (Print Publication: 2024).
DOI: 10.1371/journal.pone.0300069
Abstrakt: 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.
Competing Interests: The authors have no conflicts of interest to declare
(Copyright: © 2024 Dijk et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)
Databáze: MEDLINE
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