Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2020 May 14;15(5):e0233086.
doi: 10.1371/journal.pone.0233086. eCollection 2020.

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

B van Dijk  1 , K J H Allen  2 , M Helal  2 , H C Vogely  1 , M G E H Lam  3 , J M H de Klerk  4 , H Weinans  1   5 , B C H van der Wal  1 , E Dadachova  2
Affiliations

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

B van Dijk et al. PLoS One. .

Abstract

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 213Bi-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.

PubMed Disclaimer

Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

Fig 1
Fig 1. Susceptibility of planktonic S. aureus (MRSA) to beta and “short and long-lived” alpha radiation measured by CFU/ml for survivability (A,C,E) and XTT reduction assay for the metabolic activity (B,D,F).
Increasing doses of RIT with specific anti-WTA 4497 antibodies and non-specific antibodies Palivizumab labeled with 177Lu (A,B), 225Ac (C,D) and 213Bi (E,F). Treatment results were compared to unlabeled 4497 mAb,Palivizumab, and iodine controls. Each data point represents the average of two measurements.
Fig 2
Fig 2. Susceptibility of S. aureus (MRSA) biofilm to beta and “short and long-lived” alpha radiation measured by CFU/ml for survivability (A,C,E) and XTT reduction assay for the metabolic activity (B,D,F).
Increasing doses of RIT with specific anti-WTA 4497 antibodies and non-specific antibodies Palivizumab labeled with 177Lu (A,B), 225Ac (C,D) and 213Bi (E,F). Treatment results were compared to unlabeled 4497 mAb,Palivizumab, and iodine controls. Each data point represents the average of two measurements.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Parvizi J, Jacovides C, Zmistowski B, Jung KA. 2011. Definition of periprosthetic joint infection: Is there a consensus?. Clinical Orthopaedics and Related Research p. 3022–3030. 10.1007/s11999-011-1971-2 - DOI - PMC - PubMed
    1. Zimmerli W, Moser C. 2012. Pathogenesis and treatment concepts of orthopaedic biofilm infections. FEMS Immunol Med Microbiol 65:158–168. 10.1111/j.1574-695X.2012.00938.x - DOI - PubMed
    1. Larson SM, Carrasquillo JA, Cheung NK PO. Radioimmunotherapy of human tumours. Nat Rev Cancer 2015. June;15(6)347–60. 10.1038/nrc3925 - DOI - PMC - PubMed
    1. Dadachova E., Nakouzi A., Bryan R., and Casadevall A. Ionizing radiation delivered by specific antibody is therapeutic against a fungal infection. Proc Natl Acad Sci U S A. 100, p. 10942–10947 (2003) 10.1073/pnas.1731272100 - DOI - PMC - PubMed
    1. Helal M, Dadachova E. 2018. Radioimmunotherapy as a Novel Approach in HIV, Bacterial, and Fungal Infectious Diseases 33:1–6. - PMC - PubMed

Publication types

MeSH terms

Grants and funding

This research was funded by Health Holland, which is non for profit organization, financed by the Netherlands Organization for Scientific Research (NWO), Grant number LSHM-17026. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.