Evidence of Staphylococcus Aureus Deformation, Proliferation, and Migration in Canaliculi of Live Cortical Bone in Murine Models of Osteomyelitis.
Evidence of Staphylococcus Aureus Deformation, Proliferation, and Migration in Canaliculi of Live Cortical Bone in Murine Models of Osteomyelitis.
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DOI：
10.1002/jbmr.3055
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发表时间：
2017-05
期刊：
影响因子：
--
通讯作者：
Schwarz EM
中科院分区：
文献类型：
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作者：
de Mesy Bentley KL;Trombetta R;Nishitani K;Bello-Irizarry SN;Ninomiya M;Zhang L;Chung HL;McGrath JL;Daiss JL;Awad HA;Kates SL;Schwarz EM
虽然金黄色葡萄球菌骨髓炎被认为是无法治愈的，但活皮质骨中的主要细菌库仍然未知。除了坏死组织和植入物上的生物膜细菌外，研究还表明成骨细胞和骨细胞的细胞内感染是慢性骨髓炎的机制之一。因此，我们进行了首次系统透射电子显微镜（TEM）研究，以正式定义慢性感染小鼠（Balb/c J）长骨组织中金黄色葡萄球菌的主要储存库。尽管罕见，但还是发现了定植成骨细胞的证据。相比之下，我们很容易在活皮质骨的小管内观察到金黄色葡萄球菌，它以单个球菌和亚微米杆状细菌的链存在，导致骨细胞腔隙中形成生物膜。由于这些观察结果不符合金黄色葡萄球菌作为直径为 1.0-1.5 µm 的非运动球菌的预期，我们还在体内 BrdU 标记后进行了免疫电子显微镜 (IEM)，以评估细菌增殖在微管侵入中的作用。结果表明，变形细菌：1）通过不对称二元裂变进入小管； 2) 通过前缘的增殖向骨细胞腔隙迁移。其他体外研究证实金黄色葡萄球菌可通过 0.5 µm 多孔膜迁移。总的来说，这些发现定义了一种新的骨感染机制，并为为什么金黄色葡萄球菌植入相关的骨组织感染如此难以治疗提供了可能的新见解。
While Staphylococcus aureus osteomyelitis is considered to be incurable, the major bacterial reservoir in live cortical bone has remained unknown. In addition to biofilm bacteria on necrotic tissue and implants, studies have implicated intracellular infection of osteoblasts and osteocytes as a mechanism of chronic osteomyelitis. Thus, we performed the first systematic transmission electron microscopy (TEM) studies to formally define major reservoirs of S. aureus in chronically infected mouse (Balb/c J) long bone tissue. Although rare, evidence of colonized osteoblasts was found. In contrast, we readily observed S. aureus within canaliculi of live cortical bone, which existed as chains of individual cocci and submicron rod-shaped bacteria leading to biofilm formation in osteocyte lacunae. As these observations do not conform to the expectations of S. aureus as non-motile cocci 1.0–1.5 µm in diameter, we also performed immunoelectron microscopy (IEM) following in vivo BrdU labeling to assess the role of bacterial proliferation in canalicular invasion. The results suggest that the deformed bacteria: 1) enter canaliculi via asymmetric binary fission; and 2) migrate toward osteocyte lacunae via proliferation at the leading edge. Additional in vitro studies confirmed S. aureus migration through a 0.5 µm porous membrane. Collectively, these findings define a novel mechanism of bone infection, and provide possible new insight as to why S. aureus implant related infections of bone tissue are so challenging to treat.