title: A novel mouse model of soft-tissue infection using bioluminescence imaging allows noninvasive, real-time monitoring of bacterial growth.
abstract: Musculoskeletal infections, including surgical-site and implant-associated infections, often cause progressive inflammation and destroy areas of the soft tissue. Treating infections, especially those caused by multi-antibiotic resistant bacteria such as methicillin-resistant Staphylococcus aureus (MRSA) remains a challenge. Although there are a few animal models that enable the quantitative evaluation of infection in soft tissues, these models are not always reproducible or sustainable. Here, we successfully established a real-time, in vivo, quantitative mouse model of soft-tissue infection in the superficial gluteus muscle (SGM) using bioluminescence imaging. A bioluminescent strain of MRSA was inoculated into the SGM of BALB/c adult male mice, followed by sequential measurement of bacterial photon intensity and serological and histological analyses of the mice. The mean photon intensity in the mice peaked immediately after inoculation and remained stable until day 28. The serum levels of interleukin-6, interleukin-1 and C-reactive protein at 12 hours after inoculation were significantly higher than those prior to inoculation, and the C-reactive protein remained significantly elevated until day 21. Histological analyses showed marked neutrophil infiltration and abscesses containing necrotic and fibrous tissues in the SGM. With this SGM mouse model, we successfully visualized and quantified stable bacterial growth over an extended period of time with bioluminescence imaging, which allowed us to monitor the process of infection without euthanizing the experimental animals. This model is applicable to in vivo evaluations of the long-term efficacy of novel antibiotics or antibacterial implants.
authors.affiliation: Department of Orthopedic Surgery, School of Medicine, Keio University, Shinjuku, Tokyo, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Yoshioka
authors.affiliation: Department of Orthopedic Surgery, School of Medicine, Keio University, Shinjuku, Tokyo, Japan; Kanagawa Academy of Science and Technology (KAST), Kawasaki, Kanagawa, Japan.
authors.forename: Ken
authors.initials: K
authors.lastname: Ishii
authors.affiliation: Department of Orthopedic Surgery, School of Medicine, Keio University, Shinjuku, Tokyo, Japan.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Kuramoto
authors.affiliation: Department of Microbiology and Immunology, School of Medicine, Keio University, Shinjuku, Tokyo, Japan; Core Research for Evolutional Science and Technology (CREST), Japan Science and Technology Agency (JST), Tokyo, Japan; Department of Molecular Immunology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Shigenori
authors.initials: S
authors.lastname: Nagai
authors.affiliation: Department of Orthopedic Surgery, School of Medicine, Keio University, Shinjuku, Tokyo, Japan.
authors.forename: Haruki
authors.initials: H
authors.lastname: Funao
authors.affiliation: Department of Orthopedic Surgery, School of Medicine, Keio University, Shinjuku, Tokyo, Japan.
authors.forename: Hiroko
authors.initials: H
authors.lastname: Ishihama
authors.affiliation: Department of Orthopedic Surgery, School of Medicine, Keio University, Shinjuku, Tokyo, Japan.
authors.forename: Yuta
authors.initials: Y
authors.lastname: Shiono
authors.affiliation: Department of Pathology, School of Medicine, Keio University, Shinjuku, Tokyo, Japan.
authors.forename: Aya
authors.initials: A
authors.lastname: Sasaki
authors.affiliation: Department of Applied Chemistry, School of Science and Technology, Meiji University, Kawasaki, Kanagawa, Japan; Kanagawa Academy of Science and Technology (KAST), Kawasaki, Kanagawa, Japan.
authors.forename: Mamoru
authors.initials: M
authors.lastname: Aizawa
authors.affiliation: Department of Pathology, School of Medicine, Keio University, Shinjuku, Tokyo, Japan.
authors.forename: Yasunori
authors.initials: Y
authors.lastname: Okada
authors.affiliation: Department of Microbiology and Immunology, School of Medicine, Keio University, Shinjuku, Tokyo, Japan; Laboratory for Immune Cell System, RIKEN Center for Integrative Medical Sciences (IMS), Yokohama, Kanagawa, Japan.
authors.forename: Shigeo
authors.initials: S
authors.lastname: Koyasu
authors.affiliation: Department of Orthopedic Surgery, School of Medicine, Keio University, Shinjuku, Tokyo, Japan.
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Toyama
authors.affiliation: Department of Orthopedic Surgery, School of Medicine, Keio University, Shinjuku, Tokyo, Japan.
authors.forename: Morio
authors.initials: M
authors.lastname: Matsumoto
mesh_terms: D000818:Animals; D003952:Diagnostic Imaging; D004195:Disease Models, Animal; D008163:Luminescent Measurements; D055624:Methicillin-Resistant Staphylococcus aureus / Q000254:growth & development / Q000302:isolation & purification* / Q000472:pathogenicity; D051379:Mice; D008807:Mice, Inbred BALB C; D018461:Soft Tissue Infections / Q000175:diagnosis* / Q000382:microbiology / Q000473:pathology; D013203:Staphylococcal Infections / Q000175:diagnosis* / Q000382:microbiology / Q000473:pathology; D013211:Staphylococcus aureus / Q000254:growth & development / Q000302:isolation & purification* / Q000472:pathogenicity