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Radioimmunotherapy of methicillin-resistant Staphylococcus aureus in planktonic state and biofilms

BACKGROUND: Implant associated infections such as periprosthetic joint infections are difficult to treat as the bacteria form a biofilm on the prosthetic material. This biofilm complicates surgical and antibiotic treatment. With rising antibiotic resistance, alternative treatment options are needed...

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Autores principales: van Dijk, B., Allen, K. J. H., Helal, M., Vogely, H. C., Lam, M. G. E. H., de Klerk, J. M. H., Weinans, H., van der Wal, B. C. H., Dadachova, E.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7224548/
https://www.ncbi.nlm.nih.gov/pubmed/32407350
http://dx.doi.org/10.1371/journal.pone.0233086
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author van Dijk, B.
Allen, K. J. H.
Helal, M.
Vogely, H. C.
Lam, M. G. E. H.
de Klerk, J. M. H.
Weinans, H.
van der Wal, B. C. H.
Dadachova, E.
author_facet van Dijk, B.
Allen, K. J. H.
Helal, M.
Vogely, H. C.
Lam, M. G. E. H.
de Klerk, J. M. H.
Weinans, H.
van der Wal, B. C. H.
Dadachova, E.
author_sort van Dijk, B.
collection PubMed
description BACKGROUND: Implant associated infections such as periprosthetic joint infections are difficult to treat as the bacteria form a biofilm on the prosthetic material. This biofilm complicates surgical and antibiotic treatment. With rising antibiotic resistance, alternative treatment options are needed to treat these infections in the future. The aim of this article is to provide proof-of-principle data required for further development of radioimmunotherapy for non-invasive treatment of implant associated infections. METHODS: Planktonic cells and biofilms of Methicillin-resistant staphylococcus aureus are grown and treated with radioimmunotherapy. The monoclonal antibodies used, target wall teichoic acids that are cell and biofilm specific. Three different radionuclides in different doses were used. Viability and metabolic activity of the bacterial cells and biofilms were measured by CFU dilution and XTT reduction. RESULTS: Alpha-RIT with Bismuth-213 showed significant and dose dependent killing in both planktonic MRSA and biofilm. When planktonic bacteria were treated with 370 kBq of (213)Bi-RIT 99% of the bacteria were killed. Complete killing of the bacteria in the biofilm was seen at 185 kBq. Beta-RIT with Lutetium-177 and Actinium-225 showed little to no significant killing. CONCLUSION: Our results demonstrate the ability of specific antibodies loaded with an alpha-emitter Bismuth-213 to selectively kill staphylococcus aureus cells in vitro in both planktonic and biofilm state. RIT could therefore be a potentially alternative treatment modality against planktonic and biofilm-related microbial infections.
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spelling pubmed-72245482020-06-01 Radioimmunotherapy of methicillin-resistant Staphylococcus aureus in planktonic state and biofilms van Dijk, B. Allen, K. J. H. Helal, M. Vogely, H. C. Lam, M. G. E. H. de Klerk, J. M. H. Weinans, H. van der Wal, B. C. H. Dadachova, E. PLoS One Research Article BACKGROUND: Implant associated infections such as periprosthetic joint infections are difficult to treat as the bacteria form a biofilm on the prosthetic material. This biofilm complicates surgical and antibiotic treatment. With rising antibiotic resistance, alternative treatment options are needed to treat these infections in the future. The aim of this article is to provide proof-of-principle data required for further development of radioimmunotherapy for non-invasive treatment of implant associated infections. METHODS: Planktonic cells and biofilms of Methicillin-resistant staphylococcus aureus are grown and treated with radioimmunotherapy. The monoclonal antibodies used, target wall teichoic acids that are cell and biofilm specific. Three different radionuclides in different doses were used. Viability and metabolic activity of the bacterial cells and biofilms were measured by CFU dilution and XTT reduction. RESULTS: Alpha-RIT with Bismuth-213 showed significant and dose dependent killing in both planktonic MRSA and biofilm. When planktonic bacteria were treated with 370 kBq of (213)Bi-RIT 99% of the bacteria were killed. Complete killing of the bacteria in the biofilm was seen at 185 kBq. Beta-RIT with Lutetium-177 and Actinium-225 showed little to no significant killing. CONCLUSION: Our results demonstrate the ability of specific antibodies loaded with an alpha-emitter Bismuth-213 to selectively kill staphylococcus aureus cells in vitro in both planktonic and biofilm state. RIT could therefore be a potentially alternative treatment modality against planktonic and biofilm-related microbial infections. Public Library of Science 2020-05-14 /pmc/articles/PMC7224548/ /pubmed/32407350 http://dx.doi.org/10.1371/journal.pone.0233086 Text en © 2020 van Dijk et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
van Dijk, B.
Allen, K. J. H.
Helal, M.
Vogely, H. C.
Lam, M. G. E. H.
de Klerk, J. M. H.
Weinans, H.
van der Wal, B. C. H.
Dadachova, E.
Radioimmunotherapy of methicillin-resistant Staphylococcus aureus in planktonic state and biofilms
title Radioimmunotherapy of methicillin-resistant Staphylococcus aureus in planktonic state and biofilms
title_full Radioimmunotherapy of methicillin-resistant Staphylococcus aureus in planktonic state and biofilms
title_fullStr Radioimmunotherapy of methicillin-resistant Staphylococcus aureus in planktonic state and biofilms
title_full_unstemmed Radioimmunotherapy of methicillin-resistant Staphylococcus aureus in planktonic state and biofilms
title_short Radioimmunotherapy of methicillin-resistant Staphylococcus aureus in planktonic state and biofilms
title_sort radioimmunotherapy of methicillin-resistant staphylococcus aureus in planktonic state and biofilms
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7224548/
https://www.ncbi.nlm.nih.gov/pubmed/32407350
http://dx.doi.org/10.1371/journal.pone.0233086
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