Electronic Thesis and Dissertation Repository

Thesis Format

Integrated Article

Degree

Master of Science

Program

Surgery

Supervisor

Vasarhelyi, Edward M.

2nd Supervisor

Heinrichs, David E.

Co-Supervisor

Abstract

The most challenging complication after total joint replacement is the periprosthetic joint infection (PJI). Staphylococcus aureus is a commensal bacterium and a human pathogen. It is responsible for more than half of the PJI. We demonstrated that synovial fluid has antimicrobial properties against S. aureus and the iron restriction is one of the mechanisms used for the host to prevent bacterial growth, and is even able to increase killing of S. aureus. We have shown a clear role of transferrin as a restrictive factor in synovial fluid that functions by iron starving the bacteria and sensitizing them to killing by some other unknown factor, such as antimicrobial peptides. The development of animal models would help to improve our understanding of the pathogenesis of PJI. We also successful established an animal model of PJI, which allows the temporal observation of disease progression and gives the ability to track different bacterial mutants.

Summary for Lay Audience

The most challenging complication after total joint replacement is the periprosthetic joint infections (PJI). Staphylococcus aureus is the bacteria responsible for more than half of the infections. We demonstrated that synovial fluid has antimicrobial properties against S. aureus. The iron is the most important nutrient used for bacteria and we found that the iron restriction is one of the mechanisms used for the host to prevent bacterial growth, and is even able to increase killing of S. aureus. We have shown a clear role of one of the proteins in synovial fluid (transferrin) as a restrictive factor in synovial fluid that functions sensitizing the bacteria for killing by some other unknown factor, such as antimicrobial peptides. The development of animal models would help to improve our understanding of the PJI. We successful established an animal model of PJI, which allows the temporal observation of disease progression.

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