Radioimmunotherapy combating biofilm-associated infection in vitro
BackgroundAddressing prosthetic joint infections poses a significant challenge within orthopedic surgery, marked by elevated morbidity and mortality rates. The presence of biofilms and infections attributed to Staphylococcus aureus (S. aureus) further complicates the scenario.ObjectiveTo investigate...
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Frontiers Media S.A.
2024-11-01
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| Series: | Frontiers in Medicine |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fmed.2024.1478636/full |
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| author | Zijian Ye Berend van der Wildt F. Ruben H. A. Nurmohamed J. Fred F. Hooning van Duyvenbode Jos van Strijp H. Charles Vogely Marnix G. E. H. Lam Ekaterina Dadachova Harrie Weinans Harrie Weinans Bart C. H. van der Wal Alex J. Poot |
| author_facet | Zijian Ye Berend van der Wildt F. Ruben H. A. Nurmohamed J. Fred F. Hooning van Duyvenbode Jos van Strijp H. Charles Vogely Marnix G. E. H. Lam Ekaterina Dadachova Harrie Weinans Harrie Weinans Bart C. H. van der Wal Alex J. Poot |
| author_sort | Zijian Ye |
| collection | DOAJ |
| description | BackgroundAddressing prosthetic joint infections poses a significant challenge within orthopedic surgery, marked by elevated morbidity and mortality rates. The presence of biofilms and infections attributed to Staphylococcus aureus (S. aureus) further complicates the scenario.ObjectiveTo investigate the potential of radioimmunotherapy as an innovative intervention to tackle biofilm-associated infections.MethodsOur methodology involved employing specific monoclonal antibodies 4497-IgG1, designed for targeting wall teichoic acids found on S. aureus and its biofilm. These antibodies were linked with radionuclides actinium-225 (225Ac) and lutetium-177 (177Lu) using DOTA as a chelator. Following this, we evaluated the susceptibility of S. aureus and its biofilm to radioimmunotherapy in vitro, assessing bacterial viability and metabolic activity via colony-forming unit enumeration and xylenol tetrazolium assays.ResultsBoth [225Ac]4497-IgG1 and [177Lu]4497-IgG1 exhibited a noteworthy dose-dependent reduction in S. aureus in planktonic cultures and biofilms over a 96-h exposure period, compared to non-specific antibody control groups. Specifically, doses of 7.4 kBq and 7.4 MBq of [225Ac]4497-IgG1 and [177Lu]4497-IgG1 resulted in a four-log reduction in planktonic bacterial counts. Within biofilms, 14.8 kBq of [225Ac]4497-IgG1 and 14.8 Mbq [177Lu]4497-IgG1 led to reductions of two and four logs, respectively.ConclusionOur findings underscore the effectiveness of [225Ac]4497-IgG1 and [177Lu]4497-IgG1 antibodies in exerting dose-dependent bactericidal effects against planktonic S. aureus and biofilms in vitro. This suggests that radioimmunotherapy might serve as a promising targeted treatment approach for combating S. aureus and its biofilm. |
| format | Article |
| id | doaj-art-7bfa2e55ef9d4af1b1953d7e74f64c8d |
| institution | Kabale University |
| issn | 2296-858X |
| language | English |
| publishDate | 2024-11-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Medicine |
| spelling | doaj-art-7bfa2e55ef9d4af1b1953d7e74f64c8d2024-11-29T04:31:55ZengFrontiers Media S.A.Frontiers in Medicine2296-858X2024-11-011110.3389/fmed.2024.14786361478636Radioimmunotherapy combating biofilm-associated infection in vitroZijian Ye0Berend van der Wildt1F. Ruben H. A. Nurmohamed2J. Fred F. Hooning van Duyvenbode3Jos van Strijp4H. Charles Vogely5Marnix G. E. H. Lam6Ekaterina Dadachova7Harrie Weinans8Harrie Weinans9Bart C. H. van der Wal10Alex J. Poot11Department of Orthopaedics, University Medical Center Utrecht, Utrecht, NetherlandsDepartment of Radiology and Nuclear Medicine, University Medical Center Utrecht, Utrecht, NetherlandsDepartment of Orthopaedics, University Medical Center Utrecht, Utrecht, NetherlandsDepartment of Orthopaedics, University Medical Center Utrecht, Utrecht, NetherlandsDepartment of Medical Microbiology, University Medical Center Utrecht, Utrecht, NetherlandsDepartment of Orthopaedics, University Medical Center Utrecht, Utrecht, NetherlandsDepartment of Radiology and Nuclear Medicine, University Medical Center Utrecht, Utrecht, NetherlandsCollege of Pharmacy and Nutrition, University of Saskatchewan, Saskatoon, SK, CanadaDepartment of Orthopaedics, University Medical Center Utrecht, Utrecht, NetherlandsDepartment of Biomechanical Engineering, Faculty of Mechanical Engineering, Delft University of Technology, Delft, NetherlandsDepartment of Orthopaedics, University Medical Center Utrecht, Utrecht, NetherlandsDepartment of Radiology and Nuclear Medicine, University Medical Center Utrecht, Utrecht, NetherlandsBackgroundAddressing prosthetic joint infections poses a significant challenge within orthopedic surgery, marked by elevated morbidity and mortality rates. The presence of biofilms and infections attributed to Staphylococcus aureus (S. aureus) further complicates the scenario.ObjectiveTo investigate the potential of radioimmunotherapy as an innovative intervention to tackle biofilm-associated infections.MethodsOur methodology involved employing specific monoclonal antibodies 4497-IgG1, designed for targeting wall teichoic acids found on S. aureus and its biofilm. These antibodies were linked with radionuclides actinium-225 (225Ac) and lutetium-177 (177Lu) using DOTA as a chelator. Following this, we evaluated the susceptibility of S. aureus and its biofilm to radioimmunotherapy in vitro, assessing bacterial viability and metabolic activity via colony-forming unit enumeration and xylenol tetrazolium assays.ResultsBoth [225Ac]4497-IgG1 and [177Lu]4497-IgG1 exhibited a noteworthy dose-dependent reduction in S. aureus in planktonic cultures and biofilms over a 96-h exposure period, compared to non-specific antibody control groups. Specifically, doses of 7.4 kBq and 7.4 MBq of [225Ac]4497-IgG1 and [177Lu]4497-IgG1 resulted in a four-log reduction in planktonic bacterial counts. Within biofilms, 14.8 kBq of [225Ac]4497-IgG1 and 14.8 Mbq [177Lu]4497-IgG1 led to reductions of two and four logs, respectively.ConclusionOur findings underscore the effectiveness of [225Ac]4497-IgG1 and [177Lu]4497-IgG1 antibodies in exerting dose-dependent bactericidal effects against planktonic S. aureus and biofilms in vitro. This suggests that radioimmunotherapy might serve as a promising targeted treatment approach for combating S. aureus and its biofilm.https://www.frontiersin.org/articles/10.3389/fmed.2024.1478636/fullradioimmunotherapyStaphylococcus aureusbiofilmantibodiesinfectionwall teichoic acids |
| spellingShingle | Zijian Ye Berend van der Wildt F. Ruben H. A. Nurmohamed J. Fred F. Hooning van Duyvenbode Jos van Strijp H. Charles Vogely Marnix G. E. H. Lam Ekaterina Dadachova Harrie Weinans Harrie Weinans Bart C. H. van der Wal Alex J. Poot Radioimmunotherapy combating biofilm-associated infection in vitro Frontiers in Medicine radioimmunotherapy Staphylococcus aureus biofilm antibodies infection wall teichoic acids |
| title | Radioimmunotherapy combating biofilm-associated infection in vitro |
| title_full | Radioimmunotherapy combating biofilm-associated infection in vitro |
| title_fullStr | Radioimmunotherapy combating biofilm-associated infection in vitro |
| title_full_unstemmed | Radioimmunotherapy combating biofilm-associated infection in vitro |
| title_short | Radioimmunotherapy combating biofilm-associated infection in vitro |
| title_sort | radioimmunotherapy combating biofilm associated infection in vitro |
| topic | radioimmunotherapy Staphylococcus aureus biofilm antibodies infection wall teichoic acids |
| url | https://www.frontiersin.org/articles/10.3389/fmed.2024.1478636/full |
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