A humanized mouse model for investigating Staphylococcus aureus implant-associated infections

AO Trauma

Background

Staphylococcus aureus, continues to be the leading cause of implant-associated osteomyelitis, including fracture related infections (FRI) and peri-prosthetic joint infection (PJI). To date, no vaccine for this important pathogen exists. As the unique specificity of S. aureus as a human pathogen becomes better understood, it seems that reliance on murine models to produce pre-clinical data presents many shortcomings and may have contributed to previous failures in vaccine development.

 

 

Goal

Develop a humanized mouse model of osteomyelitis.

 

Results

Immunodeficient non-obese diabetic (NOD)–scid IL2Rγnull (NSG) mice are engrafted with human hematopoietic stem cells (HSC), and subjected to S. aureus transtibial implant-associated osteomyelitis.  Interestingly, we observed that humanized mice have: 1) increased weight loss, staphylococcal abscess colonies (SACs), and extensive osteolysis during MRSA infection, 2) increased S. aureus dissemination to distant organs, 3) more severe S. aureus bacteraemia resulting from osteomyelitis when human T-cell numbers are low. This study presents significant step towards an appropriate animal model for studying a human-specific pathogen such as S. aureus


  • Partner

    Muthukrishnan G (PhD), University of Rochester, USA

    Schwarz E (Prof), University of Rochester, USA

    Daiss J (PhD), University of Rochester, USA

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