Establishment of a Real-Time, Quantitative, and Reproducible Mouse Model of Staphylococcus Osteomyelitis Using Bioluminescence Imaging

Abstract

Osteomyelitis remains a serious problem in the orthopedic field. There are only a few animal models in which the quantity and distribution of bacteria can be reproducibly traced. Here, we established a real-time quantitative mouse model of osteomyelitis using bioluminescence imaging (BLI) without sacrificing the animals. A bioluminescent strain of Staphylococcus aureus was inoculated into the femurs of mice. The bacterial photon intensity (PI) was then sequentially measured by BLI. Serological and histological analyses of the mice were performed. The mean PI peaked at 3 days, and stable signals were maintained for over 3 months after inoculation. The serum levels of interleukin-6, interleukin-1␤, and C-reactive protein were significantly higher in the infected mice than in the control mice on day 7. The serum monocyte chemotactic protein 1 level was also significantly higher in the infected group at 12 h than in the control group. A significantly higher proportion of granulocytes was detected in the peripheral blood of the infected group after day 7. Additionally, both acute and chronic histological manifestations were observed in the infected group. This model is useful for elucidating the pathophysiology of both acute and chronic osteomyelitis and to assess the effects of novel antibiotics or antibacterial implants.

Staphylococcus aureus-dependent septic arthritis in murine knee joints: local immune response and beneficial effects of vaccination

“…All the studies which investigated this issue used infection models based either on bone implants which were previously coated with bacteria777879 or with direct deposition of bacteria on bones8081. In both cases biofilm formation in situ and, therefore, its analysis and quantification was facilitated by the experimental approach used.…”

A Novel Mouse Model of Soft-Tissue Infection Using Bioluminescence Imaging Allows Noninvasive, Real-Time Monitoring of Bacterial Growth

“…Models of bone or joint infection are commonly used to study musculoskeletal infections [2], [5], [21], [25]. A few animal models have been reported for soft tissue and skin infection, including the flank [4], [18], thigh [1], [8], and subcutaneous areas [9].…”

Scaffold-based Anti-infection Strategies in Bone Repair

“…This heterogeneity may be a possible explanation for the large variability between bacterial counts and bioluminescent signal. The use of bioluminescent bacteria has been successfully established in vivo in the context of osteomyelitis 36,42 , suggesting that this technology could be adaptable to monitoring scaffold-associated infections in bone repair. Nevertheless, genetic modification of bacteria through bioluminescent gene insertion could reduce the virulence of the clinically isolated strains, which could complicate the evaluation of infection resistant materials.…”