2020 John Charnley Award: The antimicrobial potential of bacteriophage-derived lysin in a murine debridement, antibiotics, and implant retention model of prosthetic joint infection

Bone Joint J. 2020 Jul;102-B(7_Supple_B):3-10. doi: 10.1302/0301-620X.102B7.BJJ-2019-1590.R1.

Abstract

Aims: Current treatments of prosthetic joint infection (PJI) are minimally effective against Staphylococcus aureus biofilm. A murine PJI model of debridement, antibiotics, and implant retention (DAIR) was used to test the hypothesis that PlySs2, a bacteriophage-derived lysin, can target S. aureus biofilm and address the unique challenges presented in this periprosthetic environment.

Methods: The ability of PlySs2 and vancomycin to kill biofilm and colony-forming units (CFUs) on orthopaedic implants were compared using in vitro models. An in vivo murine PJI model of DAIR was used to assess the efficacy of a combination of PlySs2 and vancomycin on periprosthetic bacterial load.

Results: PlySs2 treatment reduced 99% more CFUs and 75% more biofilm compared with vancomycin in vitro. A combination of PlySs2 and vancomycin in vivo reduced the number of CFUs on the surface of implants by 92% and in the periprosthetic tissue by 88%.

Conclusion: PlySs2 lysin was able to reduce biofilm, target planktonic bacteria, and work synergistically with vancomycin in our in vitro models. A combination of PlySs2 and vancomycin also reduced bacterial load in periprosthetic tissue and on the surface of implants in a murine model of DAIR treatment for established PJI. Cite this article: Bone Joint J 2020;102-B(7 Supple B):3-10.

Keywords: Bacteriophage; Biofilm; DAIR; Infection; Lysin; Planktonic; PlySs2; Prosthetic Joint Infection; Staphylococcus aureus.

MeSH terms

  • Animals
  • Anti-Bacterial Agents / pharmacology
  • Bacteriolysis
  • Bacteriophages*
  • Biofilms
  • Colony Count, Microbial
  • Debridement
  • Disease Models, Animal
  • Enzymes / pharmacology*
  • In Vitro Techniques
  • Mice, Inbred C57BL
  • Prosthesis-Related Infections / microbiology
  • Prosthesis-Related Infections / therapy*
  • Staphylococcal Infections / therapy*
  • Vancomycin / pharmacology

Substances

  • Anti-Bacterial Agents
  • Enzymes
  • lysin, streptococcus bacteriophage
  • Vancomycin