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

PLoS One. 2020 May 14;15(5):e0233086. doi: 10.1371/journal.pone.0233086. eCollection 2020.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actinium / therapeutic use
  • Antibodies, Monoclonal / therapeutic use
  • Biofilms / growth & development
  • Biofilms / radiation effects
  • Bismuth / therapeutic use
  • Humans
  • In Vitro Techniques
  • Lutetium / therapeutic use
  • Methicillin-Resistant Staphylococcus aureus* / immunology
  • Methicillin-Resistant Staphylococcus aureus* / radiation effects
  • Plankton / growth & development
  • Plankton / radiation effects
  • Proof of Concept Study
  • Prosthesis-Related Infections / radiotherapy*
  • Radioimmunotherapy*
  • Radioisotopes / therapeutic use
  • Staphylococcal Infections / radiotherapy*
  • Teichoic Acids / immunology

Substances

  • Actinium-225
  • Antibodies, Monoclonal
  • Bismuth-213
  • Radioisotopes
  • Teichoic Acids
  • Lutetium
  • Lutetium-177
  • Actinium
  • Bismuth

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.