A novel mouse model of soft-tissue infection using bioluminescence imaging allows noninvasive, real-time monitoring of bacterial growth.
A novel mouse model of soft-tissue infection using bioluminescence imaging allows noninvasive, real-time monitoring of bacterial growth.
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DOI：
10.1371/journal.pone.0106367
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Matsumoto M
中科院分区：
文献类型：
--
作者：
Yoshioka K;Ishii K;Kuramoto T;Nagai S;Funao H;Ishihama H;Shiono Y;Sasaki A;Aizawa M;Okada Y;Koyasu S;Toyama Y;Matsumoto M
肌肉骨骼感染，包括植入部位和植入物相关感染，通常会导致进行性炎症并破坏软组织区域。治疗感染，特别是由耐甲氧西林金黄色葡萄球菌（MRSA）等多重抗生素耐药细菌引起的感染仍然是一个挑战。虽然有一些动物模型能够定量评价软组织感染，但这些模型并不总是可重复或可持续的。在这里，我们成功地建立了一个实时的，在体内，定量的软组织感染的小鼠模型，在臀浅肌（SGM）使用生物发光成像。将MRSA的生物发光菌株接种到BALB/c成年雄性小鼠的SGM中，随后连续测量细菌光子强度并对小鼠进行血清学和组织学分析。小鼠的平均光子强度在接种后立即达到峰值，并保持稳定，直到第28天。接种后12 h血清白细胞介素-6、白细胞介素-1和C反应蛋白水平均显著高于接种前，且C反应蛋白持续显著升高至第21天。组织学分析显示SGM中有明显的中性粒细胞浸润和含有坏死和纤维组织的水肿。通过这种SGM小鼠模型，我们成功地通过生物发光成像在较长时间内可视化和量化了稳定的细菌生长，这使我们能够在不对实验动物实施安乐死的情况下监测感染过程。该模型适用于新型抗生素或抗菌植入物长期有效性的体内评价。
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.
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