A novel mouse model of soft-tissue infection using bioluminescence imaging allows noninvasive, real-time monitoring of bacterial growth

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 (M...

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Veröffentlicht in:PloS one 2014-09, Vol.9 (9), p.e106367-e106367
Hauptverfasser: Yoshioka, Kenji, Ishii, Ken, Kuramoto, Tetsuya, Nagai, Shigenori, Funao, Haruki, Ishihama, Hiroko, Shiono, Yuta, Sasaki, Aya, Aizawa, Mamoru, Okada, Yasunori, Koyasu, Shigeo, Toyama, Yoshiaki, Matsumoto, Morio
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container_volume 9
creator Yoshioka, Kenji
Ishii, Ken
Kuramoto, Tetsuya
Nagai, Shigenori
Funao, Haruki
Ishihama, Hiroko
Shiono, Yuta
Sasaki, Aya
Aizawa, Mamoru
Okada, Yasunori
Koyasu, Shigeo
Toyama, Yoshiaki
Matsumoto, Morio
description 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.
doi_str_mv 10.1371/journal.pone.0106367
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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. 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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. 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subjects Abscesses
Animal models
Animal tissues
Animals
Antibiotic resistance
Antibiotics
Bacteria
Bacterial infections
Biology and Life Sciences
Bioluminescence
C-reactive protein
Diagnostic Imaging
Disease Models, Animal
Drug resistance
Imaging
Infections
Infiltration
Inoculation
Interleukin 1
Interleukin 6
Joint surgery
Luminescent Measurements
Medicine and Health Sciences
Methicillin
Methicillin-Resistant Staphylococcus aureus - growth & development
Methicillin-Resistant Staphylococcus aureus - isolation & purification
Methicillin-Resistant Staphylococcus aureus - pathogenicity
Mice
Mice, Inbred BALB C
Muscles
Quantitative analysis
Real time
Research and Analysis Methods
Rodents
Science
Serum levels
Soft Tissue Infections - diagnosis
Soft Tissue Infections - microbiology
Soft Tissue Infections - pathology
Soft tissues
Staphylococcal Infections - diagnosis
Staphylococcal Infections - microbiology
Staphylococcal Infections - pathology
Staphylococcus aureus
Staphylococcus aureus - growth & development
Staphylococcus aureus - isolation & purification
Staphylococcus aureus - pathogenicity
Studies
Surgery
Surgical implants
Tissues
title A novel mouse model of soft-tissue infection using bioluminescence imaging allows noninvasive, real-time monitoring of bacterial growth
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