Staphylococcus aureus isolates from chronic osteomyelitis are characterized by high host cell invasion and intracellular adaptation, but still induce inflammation
Staphylococcus aureus isolates from chronic osteomyelitis are characterized by high host cell invasion and intracellular adaptation, but still induce inflammation
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DOI：
10.1016/j.ijmm.2014.07.013
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发表时间：
2014-11-01
影响因子：
4.1
通讯作者：
Tuchscherr, Lorena
中科院分区：
文献类型：
--
作者：
Kalinka, Julia;Hachmeister, Marie;Tuchscherr, Lorena
骨髓炎是一种严重的骨炎症性疾病，主要由金黄色葡萄球菌引起。特别是，骨感染很难治疗，并且尽管进行了抗菌治疗，仍可能发展成慢性病程，且复发率很高。葡萄球菌与骨组织的复杂相互作用以及细菌侵入宿主细胞的能力被认为决定了感染的严重程度。然而，尚未明确确定导致骨髓炎发病机制的细菌毒力因子。本研究的目的是检测与骨髓炎相关并导致慢性感染过程的金黄色葡萄球菌毒力因子。为此，我们收集了 41 株金黄色葡萄球菌分离株，其中 11 株来自急性骨髓炎（感染期小于 2 个月），10 株来自慢性骨髓炎（感染期超过 12 个月），10 株来自败血症，10 株来自鼻定植。对所有分离株进行基因表达和功能性体外系统分析。对骨基质的粘附测定显示所有分离株均等地与基质结构结合，但人成骨细胞的侵袭测定显示慢性骨髓炎分离株具有高侵袭能力。高入侵率无法用确定的粘附素来解释，因为所有感染菌株都表达多种粘附素，这些粘附素共同作用并决定粘附水平。宿主细胞入侵后，慢性骨髓炎分离株比所有其他分离株诱导的细胞毒性更小，并且小集落变体（SCV）形成的比例更高，这代表了长期持续期间的适应机制。急性和慢性骨髓炎的分离物强烈产生生物膜和高表达的 agr 和 sarA，调节分泌的毒力因子并诱导成骨细胞炎症反应。总之，慢性骨髓炎分离株具有高宿主细胞侵袭率、低细胞毒性以及在成骨细胞内持续和适应的能力。此外，急性和慢性骨髓炎的分离株强烈产生生物膜并诱导高水平的宿主细胞炎症，这可以解释作为长期骨感染的典型并发症而观察到的组织破坏和骨变形。 (C) 2014 年爱思唯尔有限公司。版权所有。
Osteomyelitis is a severe inflammatory disease of the bone that is mainly caused by Staphylococcus aureus. Particularly, bone infections are difficult to treat and can develop into a chronic course with a high relapsing rate despite of antimicrobial treatments. The complex interaction of staphylococci with osseous tissue and the bacterial ability to invade host cells are thought to determine the severity of infection. Yet, defined bacterial virulence factors responsible for the pathogenesis of osteomyelitis have not been clearly identified.The aim of this study was to detect S. aureus virulence factors that are associated with osteomyelitis and contribute to a chronic course of infection. To this purpose, we collected 41 S. aureus isolates, each 11 from acute osteomyelitis (infection period less than 2 months), 10 from chronic osteomyelitis (infection period more than 12 months), 10 from sepsis and 10 from nasal colonization. All isolates were analyzed for gene expression and in functional in-vitro systems. Adhesion assays to bone matrix revealed that all isolates equally bound to matrix structures, but invasion assays in human osteoblasts showed a high invasive capacity of chronic osteomyelitis isolates. The high invasion rate could not be explained by defined adhesins, as all infecting strains expressed a multitude of adhesins that act together and determine the level of adhesion. Following host cell invasion isolates from chronic osteomyelitis induced less cytotoxicity than all other isolates and a higher percentage of Small-colony-variant (SCV)-formation, which represents an adaptation mechanism during long-term persistence. Isolates from acute and chronic Osteomyelitis strongly produced biofilm and highly expressed agr and sarA that regulate secreted virulence factors and induced an inflammatory response in osteoblasts. In conclusion, chronic osteomyelitis isolates were characterized by a high host cell invasion rate, low cytotoxicity and the ability to persist and adapt within osteoblasts. Furthermore, isolates from both acute and chronic osteomyelitis strongly produced biofilm and induced high levels of host cell inflammation, which may explain tissue destruction and bone deformation observed as typical complications of long-lasting bone infections. (C) 2014 Elsevier GmbH. All rights reserved.