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
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 pipelin...
| Main Authors: | , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2022-05-01
|
| Series: | Frontiers in Cellular and Infection Microbiology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fcimb.2022.895022/full |
| _version_ | 1811233123626647552 |
|---|---|
| author | Jessica M. Gilbertie Jessica M. Gilbertie Thomas P. Schaer Julie B. Engiles Julie B. Engiles Gabriela S. Seiler Bennett L. Deddens Alicia G. Schubert Megan E. Jacob Megan E. Jacob Darko Stefanovski Gordon Ruthel Noreen J. Hickok Devorah M. Stowe Alexa Frink Lauren V. Schnabel Lauren V. Schnabel |
| author_facet | Jessica M. Gilbertie Jessica M. Gilbertie Thomas P. Schaer Julie B. Engiles Julie B. Engiles Gabriela S. Seiler Bennett L. Deddens Alicia G. Schubert Megan E. Jacob Megan E. Jacob Darko Stefanovski Gordon Ruthel Noreen J. Hickok Devorah M. Stowe Alexa Frink Lauren V. Schnabel Lauren V. Schnabel |
| author_sort | Jessica M. Gilbertie |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-12T11:16:10Z |
| format | Article |
| id | doaj.art-d29f964dd49344369715fa8855d1c898 |
| institution | Directory Open Access Journal |
| issn | 2235-2988 |
| language | English |
| last_indexed | 2024-04-12T11:16:10Z |
| publishDate | 2022-05-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cellular and Infection Microbiology |
| spelling | doaj.art-d29f964dd49344369715fa8855d1c8982022-12-22T03:35:30ZengFrontiers Media S.A.Frontiers in Cellular and Infection Microbiology2235-29882022-05-011210.3389/fcimb.2022.895022895022A Platelet-Rich Plasma-Derived Biologic Clears Staphylococcus aureus Biofilms While Mitigating Cartilage Degeneration and Joint Inflammation in a Clinically Relevant Large Animal Infectious Arthritis ModelJessica M. Gilbertie0Jessica M. Gilbertie1Thomas P. Schaer2Julie B. Engiles3Julie B. Engiles4Gabriela S. Seiler5Bennett L. Deddens6Alicia G. Schubert7Megan E. Jacob8Megan E. Jacob9Darko Stefanovski10Gordon Ruthel11Noreen J. Hickok12Devorah M. Stowe13Alexa Frink14Lauren V. Schnabel15Lauren V. Schnabel16Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC, United StatesComparative Medicine Institute, North Carolina State University, Raleigh, NC, United StatesDepartment of Clinical Studies New Bolton Center, School of Veterinary Medicine, University of Pennsylvania, Kennett Square, PA, United StatesDepartment of Clinical Studies New Bolton Center, School of Veterinary Medicine, University of Pennsylvania, Kennett Square, PA, United StatesDepartment of Pathobiology New Bolton Center, School of Veterinary Medicine, University of Pennsylvania, Kennett Square, PA, United StatesDepartment of Molecular Biomedical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC, United StatesDepartment of Molecular Biomedical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC, United StatesDepartment of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC, United StatesComparative Medicine Institute, North Carolina State University, Raleigh, NC, United StatesDepartment of Population Health and Pathobiology, College of Veterinary Medicine, North Carolina State University, Raleigh, NC, United StatesDepartment of Clinical Studies New Bolton Center, School of Veterinary Medicine, University of Pennsylvania, Kennett Square, PA, United StatesDepartment of Pathobiology New Bolton Center, School of Veterinary Medicine, University of Pennsylvania, Kennett Square, PA, United StatesDepartment of Orthopedic Surgery, Sidney Kimmel Medical College of Thomas Jefferson University, Philadelphia, PA, United StatesDepartment of Population Health and Pathobiology, College of Veterinary Medicine, North Carolina State University, Raleigh, NC, United StatesDepartment of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC, United StatesDepartment of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC, United StatesComparative Medicine Institute, North Carolina State University, Raleigh, NC, United StatesThe 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.https://www.frontiersin.org/articles/10.3389/fcimb.2022.895022/fullinfectious arthritisS. aureusbiofilmantimicrobialplateletscartilage |
| spellingShingle | Jessica M. Gilbertie Jessica M. Gilbertie Thomas P. Schaer Julie B. Engiles Julie B. Engiles Gabriela S. Seiler Bennett L. Deddens Alicia G. Schubert Megan E. Jacob Megan E. Jacob Darko Stefanovski Gordon Ruthel Noreen J. Hickok Devorah M. Stowe Alexa Frink Lauren V. Schnabel Lauren V. Schnabel 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 Frontiers in Cellular and Infection Microbiology infectious arthritis S. aureus biofilm antimicrobial platelets cartilage |
| title | 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 |
| title_full | 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 |
| title_fullStr | 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 |
| title_full_unstemmed | 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 |
| title_short | 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 |
| title_sort | 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 |
| topic | infectious arthritis S. aureus biofilm antimicrobial platelets cartilage |
| url | https://www.frontiersin.org/articles/10.3389/fcimb.2022.895022/full |
| work_keys_str_mv | AT jessicamgilbertie aplateletrichplasmaderivedbiologicclearsstaphylococcusaureusbiofilmswhilemitigatingcartilagedegenerationandjointinflammationinaclinicallyrelevantlargeanimalinfectiousarthritismodel AT jessicamgilbertie aplateletrichplasmaderivedbiologicclearsstaphylococcusaureusbiofilmswhilemitigatingcartilagedegenerationandjointinflammationinaclinicallyrelevantlargeanimalinfectiousarthritismodel AT thomaspschaer aplateletrichplasmaderivedbiologicclearsstaphylococcusaureusbiofilmswhilemitigatingcartilagedegenerationandjointinflammationinaclinicallyrelevantlargeanimalinfectiousarthritismodel AT juliebengiles aplateletrichplasmaderivedbiologicclearsstaphylococcusaureusbiofilmswhilemitigatingcartilagedegenerationandjointinflammationinaclinicallyrelevantlargeanimalinfectiousarthritismodel AT juliebengiles aplateletrichplasmaderivedbiologicclearsstaphylococcusaureusbiofilmswhilemitigatingcartilagedegenerationandjointinflammationinaclinicallyrelevantlargeanimalinfectiousarthritismodel AT gabrielasseiler aplateletrichplasmaderivedbiologicclearsstaphylococcusaureusbiofilmswhilemitigatingcartilagedegenerationandjointinflammationinaclinicallyrelevantlargeanimalinfectiousarthritismodel AT bennettldeddens aplateletrichplasmaderivedbiologicclearsstaphylococcusaureusbiofilmswhilemitigatingcartilagedegenerationandjointinflammationinaclinicallyrelevantlargeanimalinfectiousarthritismodel AT aliciagschubert aplateletrichplasmaderivedbiologicclearsstaphylococcusaureusbiofilmswhilemitigatingcartilagedegenerationandjointinflammationinaclinicallyrelevantlargeanimalinfectiousarthritismodel AT meganejacob aplateletrichplasmaderivedbiologicclearsstaphylococcusaureusbiofilmswhilemitigatingcartilagedegenerationandjointinflammationinaclinicallyrelevantlargeanimalinfectiousarthritismodel AT meganejacob aplateletrichplasmaderivedbiologicclearsstaphylococcusaureusbiofilmswhilemitigatingcartilagedegenerationandjointinflammationinaclinicallyrelevantlargeanimalinfectiousarthritismodel AT darkostefanovski aplateletrichplasmaderivedbiologicclearsstaphylococcusaureusbiofilmswhilemitigatingcartilagedegenerationandjointinflammationinaclinicallyrelevantlargeanimalinfectiousarthritismodel AT gordonruthel aplateletrichplasmaderivedbiologicclearsstaphylococcusaureusbiofilmswhilemitigatingcartilagedegenerationandjointinflammationinaclinicallyrelevantlargeanimalinfectiousarthritismodel AT noreenjhickok aplateletrichplasmaderivedbiologicclearsstaphylococcusaureusbiofilmswhilemitigatingcartilagedegenerationandjointinflammationinaclinicallyrelevantlargeanimalinfectiousarthritismodel AT devorahmstowe aplateletrichplasmaderivedbiologicclearsstaphylococcusaureusbiofilmswhilemitigatingcartilagedegenerationandjointinflammationinaclinicallyrelevantlargeanimalinfectiousarthritismodel AT alexafrink aplateletrichplasmaderivedbiologicclearsstaphylococcusaureusbiofilmswhilemitigatingcartilagedegenerationandjointinflammationinaclinicallyrelevantlargeanimalinfectiousarthritismodel AT laurenvschnabel aplateletrichplasmaderivedbiologicclearsstaphylococcusaureusbiofilmswhilemitigatingcartilagedegenerationandjointinflammationinaclinicallyrelevantlargeanimalinfectiousarthritismodel AT laurenvschnabel aplateletrichplasmaderivedbiologicclearsstaphylococcusaureusbiofilmswhilemitigatingcartilagedegenerationandjointinflammationinaclinicallyrelevantlargeanimalinfectiousarthritismodel AT jessicamgilbertie plateletrichplasmaderivedbiologicclearsstaphylococcusaureusbiofilmswhilemitigatingcartilagedegenerationandjointinflammationinaclinicallyrelevantlargeanimalinfectiousarthritismodel AT jessicamgilbertie plateletrichplasmaderivedbiologicclearsstaphylococcusaureusbiofilmswhilemitigatingcartilagedegenerationandjointinflammationinaclinicallyrelevantlargeanimalinfectiousarthritismodel AT thomaspschaer plateletrichplasmaderivedbiologicclearsstaphylococcusaureusbiofilmswhilemitigatingcartilagedegenerationandjointinflammationinaclinicallyrelevantlargeanimalinfectiousarthritismodel AT juliebengiles plateletrichplasmaderivedbiologicclearsstaphylococcusaureusbiofilmswhilemitigatingcartilagedegenerationandjointinflammationinaclinicallyrelevantlargeanimalinfectiousarthritismodel AT juliebengiles plateletrichplasmaderivedbiologicclearsstaphylococcusaureusbiofilmswhilemitigatingcartilagedegenerationandjointinflammationinaclinicallyrelevantlargeanimalinfectiousarthritismodel AT gabrielasseiler plateletrichplasmaderivedbiologicclearsstaphylococcusaureusbiofilmswhilemitigatingcartilagedegenerationandjointinflammationinaclinicallyrelevantlargeanimalinfectiousarthritismodel AT bennettldeddens plateletrichplasmaderivedbiologicclearsstaphylococcusaureusbiofilmswhilemitigatingcartilagedegenerationandjointinflammationinaclinicallyrelevantlargeanimalinfectiousarthritismodel AT aliciagschubert plateletrichplasmaderivedbiologicclearsstaphylococcusaureusbiofilmswhilemitigatingcartilagedegenerationandjointinflammationinaclinicallyrelevantlargeanimalinfectiousarthritismodel AT meganejacob plateletrichplasmaderivedbiologicclearsstaphylococcusaureusbiofilmswhilemitigatingcartilagedegenerationandjointinflammationinaclinicallyrelevantlargeanimalinfectiousarthritismodel AT meganejacob plateletrichplasmaderivedbiologicclearsstaphylococcusaureusbiofilmswhilemitigatingcartilagedegenerationandjointinflammationinaclinicallyrelevantlargeanimalinfectiousarthritismodel AT darkostefanovski plateletrichplasmaderivedbiologicclearsstaphylococcusaureusbiofilmswhilemitigatingcartilagedegenerationandjointinflammationinaclinicallyrelevantlargeanimalinfectiousarthritismodel AT gordonruthel plateletrichplasmaderivedbiologicclearsstaphylococcusaureusbiofilmswhilemitigatingcartilagedegenerationandjointinflammationinaclinicallyrelevantlargeanimalinfectiousarthritismodel AT noreenjhickok plateletrichplasmaderivedbiologicclearsstaphylococcusaureusbiofilmswhilemitigatingcartilagedegenerationandjointinflammationinaclinicallyrelevantlargeanimalinfectiousarthritismodel AT devorahmstowe plateletrichplasmaderivedbiologicclearsstaphylococcusaureusbiofilmswhilemitigatingcartilagedegenerationandjointinflammationinaclinicallyrelevantlargeanimalinfectiousarthritismodel AT alexafrink plateletrichplasmaderivedbiologicclearsstaphylococcusaureusbiofilmswhilemitigatingcartilagedegenerationandjointinflammationinaclinicallyrelevantlargeanimalinfectiousarthritismodel AT laurenvschnabel plateletrichplasmaderivedbiologicclearsstaphylococcusaureusbiofilmswhilemitigatingcartilagedegenerationandjointinflammationinaclinicallyrelevantlargeanimalinfectiousarthritismodel AT laurenvschnabel plateletrichplasmaderivedbiologicclearsstaphylococcusaureusbiofilmswhilemitigatingcartilagedegenerationandjointinflammationinaclinicallyrelevantlargeanimalinfectiousarthritismodel |