Department of Oral Biology, New Jersey Dental School, University of Medicine and Dentistry of New Jersey, Newark, NJ 07103, USA.
Microb Pathog. 2011 Jul-Aug;51(1-2):22-30. doi: 10.1016/j.micpath.2011.03.005. Epub 2011 Apr 2.
Kingella kingae is an emerging pathogen causing osteoarticular infections in pediatric patients. Electron microscopy of K. kingae clinical isolates revealed the heterogeneously-sized membranous structures blebbing from the outer membrane that were classified as outer membrane vesicles (OMVs). OMVs purified from the secreted fraction of a septic arthritis K. kingae isolate were characterized. Among several major proteins, K. kingae OMVs contained virulence factors RtxA toxin and PilC2 pilus adhesin. RtxA was also found secreted as a soluble protein in the extracellular environment indicating that the bacterium may utilize different mechanisms for the toxin delivery. OMVs were shown to be hemolytic and possess some leukotoxic activity while high leukotoxicity was detected in the non-hemolytic OMV-free component of the secreted fraction. OMVs were internalized by human osteoblasts and synovial cells. Upon interaction with OMVs, the cells produced increased levels of human granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin 6 (IL-6) suggesting that these cytokines might be involved in the signaling response of infected joint and bone tissues during natural K. kingae infection. This study is the first report of OMV production by K. kingae and demonstrates that OMVs are a complex virulence factor of the organism causing cytolytic and inflammatory effects on host cells.
金氏金菌是一种新兴的病原体，可引起儿科患者的骨关节炎感染。对金氏金菌临床分离株的电子显微镜检查显示，从外膜上出芽的异质大小的膜状结构被归类为外膜囊泡（OMV）。从金氏金菌分离的脓毒性关节炎分泌部分纯化的 OMV 进行了表征。在几种主要蛋白质中，金氏金菌 OMV 含有毒力因子 RtxA 毒素和 PilC2 菌毛黏附素。还发现 RtxA 作为可溶性蛋白在细胞外环境中分泌，表明细菌可能利用不同的机制来输送毒素。OMV 具有溶血作用，并具有一些白细胞毒性活性，而在分泌部分的非溶血 OMV 无成分中检测到高白细胞毒性活性。OMV 被人成骨细胞和滑膜细胞内化。与 OMV 相互作用后，细胞产生了更高水平的人粒细胞-巨噬细胞集落刺激因子（GM-CSF）和白细胞介素 6（IL-6），表明这些细胞因子可能参与了金氏金菌自然感染过程中受感染关节和骨骼组织的信号转导反应。本研究首次报道了金氏金菌产生 OMV，并证明 OMV 是该生物体的一种复杂毒力因子，对宿主细胞具有细胞溶解和炎症作用。
