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Frontiers in cellular and infection microbiology2022; 12; 895022; doi: 10.3389/fcimb.2022.895022

A Platelet-Rich Plasma-Derived Biologic Clears Staphylococcus aureus Biofilms While Mitigating Cartilage Degeneration and Joint Inflammation in a Clinically Relevant Large Animal Infectious Arthritis Model.

Abstract: The leading cause of treatment failure in Staphylococcus aureus infections is the development of biofilms. Biofilms are highly tolerant to conventional antibiotics which were developed against planktonic cells. Consequently, there is a lack of antibiofilm agents in the antibiotic development pipeline. To address this problem, we developed a platelet-rich plasma (PRP)-derived biologic, termed BIO-PLY (for the BIOactive fraction of Platelet-rich plasma LYsate) which has potent in vitro bactericidal activity against S. aureus synovial fluid free-floating biofilm aggregates. Additional in vitro studies using equine synoviocytes and chondrocytes showed that BIO-PLY protected these cells of the joint from inflammation. The goal of this study was to test BIO-PLY for in vivo efficacy using an equine model of infectious arthritis. We found that horses experimentally infected with S. aureus and subsequently treated with BIO-PLY combined with the antibiotic amikacin (AMK) had decreased bacterial concentrations within both synovial fluid and synovial tissue and exhibited lower systemic and local inflammatory scores compared to horses treated with AMK alone. Most importantly, AMK+BIO-PLY treatment reduced the loss of infection-associated cartilage proteoglycan content in articular cartilage and decreased synovial tissue fibrosis and inflammation. Our results demonstrate the in vivo efficacy of AMK+BIO-PLY and represents a new approach to restore and potentiate antimicrobial activity against synovial fluid biofilms.
Copyright © 2022 Gilbertie, Schaer, Engiles, Seiler, Deddens, Schubert, Jacob, Stefanovski, Ruthel, Hickok, Stowe, Frink and Schnabel.
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Publication Date: 2022-05-30 PubMed ID: 35711655PubMed Central: PMC9195519DOI: 10.3389/fcimb.2022.895022Google Scholar: Lookup
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  • Journal Article
  • Research Support
  • N.I.H.
  • Extramural
  • Research Support
  • Non-U.S. Gov't

Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

This research study presents a solution to combat bacterial biofilms, which are a common reason for the failure of treating infections. The study introduces a platelet-rich plasma-derived biologic, called BIO-PLY, which effectively kills bacterias found in biofilms and protect joint cells from inflammation. In trials using horses, combining BIO-PLY with an antibiotic called amikacin resulted in significantly lower bacterial concentrations and a decrease in infection-related damage to cartilage.

Development and Rationale of BIO-PLY

  • The researchers developed a platelet-rich plasma (PRP)-derived biologic, known as BIO-PLY, to address the problems caused by biofilms. Biofilms are a collection of bacteria that are highly resistant to conventional antibiotics because these medications were designed to target free-floating (or “planktonic”) bacterial cells rather than grouped ones.
  • BIO-PLY has been found to effectively kill free-floating biofilm aggregates in synovial fluid, a lubricating fluid found in the joints.
  • Additionally, BIO-PLY was shown to protect joint cells, specifically equine synoviocytes and chondrocytes, from inflammation.

BIO-PLY and Antibiotic Effectiveness

  • The researchers then set out to test the efficacy of BIO-PLY in a real-world model, hence they used an equine model of infectious arthritis. Horses were infected experimentally and then treated with a combination of BIO-PLY and an antibiotic called amikacin.
  • Compared to horses treated only with amikacin, those that received both BIO-PLY and amikacin had lower bacterial concentrations in both synovial fluid and synovial tissue, which implies a rapid and stronger antibacterial effect.
  • The combined treatment also resulted in significantly lower scores for both systemic and local inflammation.

Cartilage Protection and Restoration

  • Besides the effective antibacterial and anti-inflammatory results, the combined treatment of BIO-PLY and amikacin also showed positive effects on the structural elements of joints.
  • Treatment with both BIO-PLY and amikacin reduced the loss of infection-related cartilage proteoglycan content in articular cartilage, a critical structural and functional component of cartilage. Therefore, it not only intercepted the infection but also protected the joint against potential structural damage.
  • The treatment also decreased fibrosis and inflammation in the synovial tissue, further indicating its potential joint-protective qualities.

Conclusion and Implications

  • The results of the study demonstrate a potential new approach to treating infections, particularly those where biofilms are involved. The researchers assert that the partnership of BIO-PLY and amikacin can potentially restore and bolster antimicrobial activity against these biofilms.
  • Not only does this combination treatment address the bacterial infection effectively, but it also actively counters inflammation and protects the structural integrity of joints. Thus, it could be a potential solution for treating infection-related conditions such as infectious arthritis.

Cite This Article

APA
Gilbertie JM, Schaer TP, Engiles JB, Seiler GS, Deddens BL, Schubert AG, Jacob ME, Stefanovski D, Ruthel G, Hickok NJ, Stowe DM, Frink A, Schnabel LV. (2022). A Platelet-Rich Plasma-Derived Biologic Clears Staphylococcus aureus Biofilms While Mitigating Cartilage Degeneration and Joint Inflammation in a Clinically Relevant Large Animal Infectious Arthritis Model. Front Cell Infect Microbiol, 12, 895022. https://doi.org/10.3389/fcimb.2022.895022

Publication

Frontiers in cellular and infection microbiology
ISSN: 2235-2988
NlmUniqueID: 101585359
Country: Switzerland
Language: English
Volume: 12
Pages: 895022

Researcher Affiliations

Gilbertie, Jessica M
  • Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC, United States.
  • Comparative Medicine Institute, North Carolina State University, Raleigh, NC, United States.
Schaer, Thomas P
  • Department of Clinical Studies New Bolton Center, School of Veterinary Medicine, University of Pennsylvania, Kennett Square, PA, United States.
Engiles, Julie B
  • Department of Clinical Studies New Bolton Center, School of Veterinary Medicine, University of Pennsylvania, Kennett Square, PA, United States.
  • Department of Pathobiology New Bolton Center, School of Veterinary Medicine, University of Pennsylvania, Kennett Square, PA, United States.
Seiler, Gabriela S
  • Department of Molecular Biomedical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC, United States.
Deddens, Bennett L
  • Department of Molecular Biomedical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC, United States.
Schubert, Alicia G
  • Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC, United States.
Jacob, Megan E
  • Comparative Medicine Institute, North Carolina State University, Raleigh, NC, United States.
  • Department of Population Health and Pathobiology, College of Veterinary Medicine, North Carolina State University, Raleigh, NC, United States.
Stefanovski, Darko
  • Department of Clinical Studies New Bolton Center, School of Veterinary Medicine, University of Pennsylvania, Kennett Square, PA, United States.
Ruthel, Gordon
  • Department of Pathobiology New Bolton Center, School of Veterinary Medicine, University of Pennsylvania, Kennett Square, PA, United States.
Hickok, Noreen J
  • Department of Orthopedic Surgery, Sidney Kimmel Medical College of Thomas Jefferson University, Philadelphia, PA, United States.
Stowe, Devorah M
  • Department of Population Health and Pathobiology, College of Veterinary Medicine, North Carolina State University, Raleigh, NC, United States.
Frink, Alexa
  • Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC, United States.
Schnabel, Lauren V
  • Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC, United States.
  • Comparative Medicine Institute, North Carolina State University, Raleigh, NC, United States.

MeSH Terms

  • Amikacin
  • Animals
  • Anti-Bacterial Agents / pharmacology
  • Anti-Bacterial Agents / therapeutic use
  • Arthritis, Infectious / drug therapy
  • Biofilms
  • Biological Products
  • Disease Models, Animal
  • Horses
  • Inflammation
  • Platelet-Rich Plasma
  • Staphylococcal Infections / drug therapy
  • Staphylococcal Infections / veterinary
  • Staphylococcus aureus

Grant Funding

  • R01 AR072513 / NIAMS NIH HHS

Conflict of Interest Statement

The contents of this manuscript are the subject of a patent filed by NC State University and the University of Pennsylvania by the authors (JG, TS, and LS). The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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