Centre for Orthopaedic & Trauma Research, Faculty of Health Sciences, University of Adelaide, Adelaide, South Australia, Australia.
Bioinformatics Hub, School of Biological Sciences, University of Adelaide, Adelaide, South Australia, Australia.
mBio. 2018 Apr 24;9(2):e00415-18. doi: 10.1128/mBio.00415-18.
Periprosthetic joint infection (PJI) is a potentially devastating complication of orthopedic joint replacement surgery. PJI with associated osteomyelitis is particularly problematic and difficult to cure. Whether viable osteocytes, the predominant cell type in mineralized bone tissue, have a role in these infections is not clear, although their involvement might contribute to the difficulty in detecting and clearing PJI. Here, using , the most common pathogen in PJI, we demonstrate intracellular infection of human-osteocyte-like cells and adaptation by forming quasi-dormant small-colony variants (SCVs). Consistent patterns of host gene expression were observed between -infected osteocyte-like cultures, an human bone infection model, and bone samples obtained from PJI patients. Finally, we confirm infection of osteocytes in clinical cases of PJI. Our findings are consistent with osteocyte infection being a feature of human PJI and suggest that this cell type may provide a reservoir for silent or persistent infection. We suggest that elucidating the molecular/cellular mechanism(s) of osteocyte-bacterium interactions will contribute to better understanding of PJI and osteomyelitis, improved pathogen detection, and treatment. Periprosthetic joint infections (PJIs) are increasing and are recognized as one of the most common modes of failure of joint replacements. Osteomyelitis arising from PJI is challenging to treat and difficult to cure and increases patient mortality 5-fold. is the most common pathogen causing PJI. PJI can have subtle symptoms and lie dormant or go undiagnosed for many years, suggesting persistent bacterial infection. Osteocytes, the major bone cell type, reside in bony caves and tunnels, the lacuno-canalicular system. We report here that can infect and reside in human osteocytes without causing cell death both experimentally and in bone samples from patients with PJI. We demonstrate that osteocytes respond to infection by the differential regulation of a large number of genes. adapts during intracellular infection of osteocytes by adopting the quasi-dormant small-colony variant (SCV) lifestyle, which might contribute to persistent or silent infection. Our findings shed new light on the etiology of PJI and osteomyelitis in general.
人工关节周围感染（PJI）是骨科关节置换手术后一种潜在的破坏性并发症。伴有骨髓炎的 PJI 尤其成问题且难以治愈。尽管骨细胞在检测和清除 PJI 方面的困难可能与其有关，但在这些感染中是否存在作为主要细胞类型的有活力的骨细胞仍不清楚。在这里，我们使用 PJI 中最常见的病原体 ，证明了人类成骨细胞样细胞的细胞内感染 ，以及通过形成准休眠小菌落变体（SCV）的适应性 。在 感染的成骨细胞样培养物、 人骨感染模型和从 PJI 患者获得的骨样本之间观察到一致的宿主基因表达模式。最后，我们确认了临床 PJI 病例中的 感染骨细胞。我们的研究结果表明，骨细胞感染是人类 PJI 的一个特征，并表明该细胞类型可能为沉默或持续感染提供一个储备库。我们建议阐明骨细胞与细菌相互作用的分子/细胞机制将有助于更好地理解 PJI 和骨髓炎、提高病原体检测和治疗效果。人工关节周围感染（PJIs）正在增加，被认为是关节置换失败的最常见方式之一。由 PJI 引起的骨髓炎很难治疗且难以治愈，会使患者死亡率增加 5 倍。 是引起 PJI 的最常见病原体。PJI 可能症状轻微，潜伏多年或未被诊断，表明存在持续的细菌感染。骨细胞是主要的骨细胞类型，位于骨腔和隧道（即，骨陷窝-小管系统）中。我们在此报告， 可以在不引起细胞死亡的情况下感染并存在于人类成骨细胞中，无论是在实验中还是在患有 PJI 的患者的骨样本中。我们证明，成骨细胞通过调节大量基因的差异表达来响应感染。 在内源性感染成骨细胞期间通过采用准休眠小菌落变体（SCV）生活方式适应，这可能有助于持续或沉默感染。我们的发现为 PJI 和骨髓炎的病因学提供了新的线索。
