Mouse model of chronic post-arthroplasty infection: noninvasive in vivo bioluminescence imaging to monitor bacterial burden for long-term study.

Mouse model of chronic post-arthroplasty infection: noninvasive in vivo bioluminescence imaging to monitor bacterial burden for long-term study.
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DOI:
10.1002/jor.21519
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发表时间:
2012-03
影响因子:
2.8
通讯作者:
Miller, Lloyd S.
Miller, Lloyd S.
中科院分区:
医学3区
文献类型:
--
作者:
Pribaz, Jonathan R.;Bernthal, Nicholas M.;Billi, Fabrizio;Cho, John S.;Ramos, Romela Irene;Guo, Yi;Cheung, Ambrose L.;Francis, Kevin P.;Miller, Lloyd S.

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关节置换术后感染是骨科手术中的一个严重问题。虽然急性感染可以通过单阶段冲洗和换药治疗,但慢性感染会导致多次再手术,延长抗生素疗程,延长残疾和更糟糕的临床结果。与以往研究急性感染的小鼠模型不同,这项工作旨在建立一种慢性关节置换术后感染的模型。为了实现这一目标,在小鼠膝关节的不锈钢植入物中接种了一种生物发光金黄色葡萄球菌菌株(1×102-1×104 CFUs),并使用体内成像监测42天的细菌负荷。比较了四种不同的金黄色葡萄球菌染色,将生物发光结构整合在抗生素选择质粒(ALC2906)、细菌染色体(Xen29和Xen40)或稳定质粒(Xen36)中。ALC2906在第10天增加了生物发光信号,之后信号变得无法检测到。相比之下,Xen29、Xen40和Xen36在42天内增加了生物发光信号,其中Xen36的信号最高。通过LysEGFP小鼠体内egfp -中性粒细胞荧光测定,ALC2906、Xen29和Xen40诱导的炎症明显高于Xen36。通过变压扫描电子显微镜确定,所有四种菌株诱导的生物膜形成相当。使用钛植入物,Xen36比Xen40具有更高的体内生物发光信号,但具有相似的生物膜形成和粘附细菌。综上所述,具有稳定生物发光结构的Xen29、Xen40,特别是Xen36,可用于长期体内监测细菌负荷和生物膜形成,以研究慢性关节置换术后感染和潜在的抗菌干预措施。
Post-arthroplasty infections are a devastating problem in orthopaedic surgery. While acute infections can be treated with a single stage washout and liner exchange, chronic infections lead to multiple reoperations, prolonged antibiotic courses, extended disability and worse clinical outcomes. Unlike previous mouse models that studied an acute infection, this work aimed to develop a model of a chronic post-arthroplasty infection. To achieve this, a stainless steel implant in the knee joints of mice was inoculated with a bioluminescent S. aureus strain (1×102–1×104 CFUs) and in vivo imaging was used to monitor the bacterial burden for 42 days. Four different S. aureus stains were compared in which the bioluminescent construct was integrated in an antibiotic selection plasmid (ALC2906), the bacterial chromosome (Xen29 and Xen40) or a stable plasmid (Xen36). ALC2906 had increased bioluminescent signals through day 10, after which the signals became undetectable. In contrast, Xen29, Xen40 and Xen36 had increased bioluminescent signals through 42 days with the highest signals observed with Xen36. ALC2906, Xen29 and Xen40 induced significantly more inflammation than Xen36 as measured by in vivo EGFP-neutrophil florescence of LysEGFP mice. All four strains induced comparable biofilm formation as determined by variable-pressure scanning electron microscopy. Using a titanium implant, Xen36 had higher in vivo bioluminescence signals than Xen40 but had similar biofilm formation and adherent bacteria. In conclusion, Xen29, Xen40 and especially Xen36, which had stable bioluminescence constructs, are feasible for long-term in vivo monitoring of bacterial burden and biofilm formation to study chronic post-arthroplasty infections and potential antimicrobial interventions.
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发表时间: 2007-10-01
影响因子: 5.3
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DOI: 10.1302/0301-620x.90b3.20155
发表时间: 2008-03-01
影响因子: --
作者:
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通讯作者: McCabe, J. P.