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Evading the host response: Staphylococcus “hiding” in cortical bone canalicular system causes increased bacterial burden
Bone Research ( IF 14.3 ) Pub Date : 2020-12-10 , DOI: 10.1038/s41413-020-00118-w
Stephen D Zoller 1 , Vishal Hegde 1 , Zachary D C Burke 1 , Howard Y Park 1 , Chad R Ishmael 1 , Gideon W Blumstein 1 , William Sheppard 1 , Christopher Hamad 1 , Amanda H Loftin 1 , Daniel O Johansen 1 , Ryan A Smith 2 , Marina M Sprague 3 , Kellyn R Hori 1, 2 , Samuel J Clarkson 2 , Rachel Borthwell 2 , Scott I Simon 4 , Jeff F Miller 5, 6 , Scott D Nelson 7 , Nicholas M Bernthal 1
Affiliation  

Extremity reconstruction surgery is increasingly performed rather than amputation for patients with large-segment pathologic bone loss. Debate persists as to the optimal void filler for this “limb salvage” surgery, whether metal or allograft bone. Clinicians focus on optimizing important functional gains for patients, and the risk of devastating implant infection has been thought to be similar regardless of implant material. Recent insights into infection pathophysiology are challenging this equipoise, however, with both basic science data suggesting a novel mechanism of infection of Staphylococcus aureus (the most common infecting agent) into the host lacunar–canaliculi network, and also clinical data revealing a higher rate of infection of allograft over metal. The current translational study was therefore developed to bridge the gap between these insights in a longitudinal murine model of infection of allograft bone and metal. Real-time Staphylococci infection characteristics were quantified in cortical bone vs metal, and both microarchitecture of host implant and presence of host immune response were assessed. An orders-of-magnitude higher bacterial burden was established in cortical allograft bone over both metal and cancellous bone. The establishment of immune-evading microabscesses was confirmed in both cortical allograft haversian canal and the submicron canaliculi network in an additional model of mouse femur bone infection. These study results reveal a mechanism by which Staphylococci evasion of host immunity is possible, contributing to elevated risks of infection in cortical bone. The presence of this local infection reservoir imparts massive clinical implications that may alter the current paradigm of osteomyelitis and bulk allograft infection treatment.



中文翻译:


逃避宿主反应:“隐藏”在皮质骨小管系统中的葡萄球菌导致细菌负担增加



对于大节段病理性骨丢失的患者,越来越多地进行肢体重建手术,而不是截肢。对于这种“保肢”手术的最佳空隙填充物,无论是金属还是同种异体移植骨,一直存在争论。临床医生专注于优化患者的重要功能增益,并且无论植入材料如何,破坏性植入物感染的风险都被认为是相似的。然而,最近对感染病理生理学的见解正在挑战这种平衡,基础科学数据表明金黄色葡萄球菌(最常见的感染因子)感染宿主腔隙-小管网络的新机制,临床数据也显示更高的感染率同种异体移植物对金属的感染。因此,目前的转化研究旨在弥合同种异体骨和金属感染的纵向小鼠模型中这些见解之间的差距。在皮质骨与金属中量化实时葡萄球菌感染特征,并评估宿主植入物的微结构和宿主免疫反应的存在。皮质同种异体移植骨中的细菌负荷比金属骨和松质骨高出几个数量级。在小鼠股骨感染的另一个模型中,在皮质同种异体移植哈弗管和亚微米小管网络中均证实了逃避免疫的微脓肿的建立。这些研究结果揭示了葡萄球菌可能逃避宿主免疫的机制,从而导致皮质骨感染风险升高。 这种局部感染库的存在具有巨大的临床意义,可能会改变目前骨髓炎和大量同种异体移植物感染治疗的模式。

更新日期:2020-12-10
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