Porphyromonas gingivalis Outer Membrane Vesicles Increase Vascular Permeability.
Porphyromonas gingivalis Outer Membrane Vesicles Increase Vascular Permeability.
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DOI：
10.1177/0022034520943187
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发表时间：
2020-12
影响因子：
7.6
通讯作者：
Murdoch C
中科院分区：
文献类型：
--
作者：
Farrugia C;Stafford GP;Murdoch C
牙周炎越来越多地与心血管和其他系统性疾病的风险增加有关。革兰氏阴性厌氧菌，牙龈卟啉单胞菌，是一种重要的牙周病原体，有几条证据将这种细菌在循环中的存在与血管疾病联系起来。牙龈卟啉单胞菌产生的外膜囊泡（OMV）已被证明在牙周炎中发挥作用，尽管迄今为止，对它们与血管系统的相互作用知之甚少;因此，本研究评估了牙龈卟啉单胞菌OMV对内皮的影响。OMV分离自野生型菌株W83和牙龈卟啉菌蛋白酶缺陷型菌株ΔK/R-ab。免疫印迹沿着冷冻EM显示牙龈卟啉菌蛋白酶在W83中表达，但在ΔK/R-ab衍生的OMV中没有，其中牙龈卟啉菌蛋白酶定位于细胞壁表面。与感染ΔK/R-ab或其OMV的内皮细胞相比，感染W83或W83衍生的OMV的汇合内皮细胞单层显示葡聚糖渗透性显著增加。此外，W83衍生的OMV诱导显着更多的血管疾病在斑马鱼幼虫全身感染模型超过72小时相比，那些注射牙龈卟啉蛋白酶缺陷OMV或控制。与这些数据一致，当通过流式细胞术检查时，人微血管内皮细胞（HMEC-1）显示细胞表面细胞间粘附分子PECAM-1（CD 31）水平的OMV相关的牙龈蛋白酶依赖性降低。这些数据首次表明，来自牙龈卟啉单胞菌的OMV介导血管渗透性增加，导致体外和体内的患病表型。此外，这些数据强烈暗示存在于OMV表面上的牙龈卟啉菌蛋白酶介导这些血管事件，最有可能是通过涉及内皮细胞-细胞粘附素如PECAM-1的蛋白水解裂解的机制。这些数据为细菌源性OMV在介导系统性疾病中的作用提供了重要证据。
Periodontitis is increasingly associated with increased risk of cardiovascular and other systemic diseases. The Gram-negative anaerobe, Porphyromonas gingivalis, is a key periodontal pathogen, and several lines of evidence link the presence of this bacterium in the circulation with vascular disease. The outer membrane vesicles (OMVs) produced by P. gingivalis have been shown to play a role in periodontitis, although, to date, little is known about their interaction with the vasculature; therefore, this study assessed the effects of P. gingivalis OMVs on the endothelium. OMVs were isolated from wild-type strain W83 and the gingipain-deficient strain ΔK/R-ab. Immunoblotting along with cryo-EM showed gingipain expression in W83 but not ΔK/R-ab-derived OMVs, where gingipains were localized to the cell wall surface. Confluent endothelial cell monolayers infected with either W83 or W83-derived OMV displayed significantly increased dextran permeability over those infected with ΔK/R-ab or its OMV. Moreover, W83-derived OMVs induced significantly more vascular disease in a zebrafish larvae systemic infection model over 72 h compared to those injected with gingipain-deficient OMVs or controls. In line with these data, human microvascular endothelial cells (HMEC-1) displayed an OMV-associated, gingipain-dependent decrease in cell surface levels of the intercellular adhesion molecule PECAM-1 (CD31) when examined by flow cytometry. These data show, for the first time, that OMVs from P. gingivalis mediate increased vascular permeability, leading to a diseased phenotype both in vitro and in vivo. Moreover, these data strongly implicate gingipains present on the OMV surface in mediating these vascular events, most likely via a mechanism that involves proteolytic cleavage of endothelial cell-cell adhesins such as PECAM-1. These data provide important evidence for the role of bacterial-derived OMVs in mediating systemic disease.
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影响因子：
3.6
作者：
Privratsky, Jamie R.;Newman, Peter J.
通讯作者：
Newman, Peter J.
影响因子：
6.5
作者：
ADES, EW;CANDAL, FJ;LAWLEY, TJ
通讯作者：
LAWLEY, TJ
影响因子：
7.6
作者：
Gustafsson, N.;Ahlqvist, J.;Levring Jaghagen, E.
通讯作者：
Levring Jaghagen, E.
影响因子：
3.1
作者：
Aduse-Opoku, J;Slaney, JM;Curtis, MA
通讯作者：
Curtis, MA
影响因子：
4.3
作者：
Loos, BG
通讯作者：
Loos, BG