SssP1, a Fimbria-like component of Streptococcus suis, binds to the vimentin of host cells and contributes to bacterial meningitis.
SssP1, a Fimbria-like component of Streptococcus suis, binds to the vimentin of host cells and contributes to bacterial meningitis.
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SssP1是猪链球菌的菌毛样成分，与宿主细胞的波形蛋白结合，导致细菌性脑膜炎。
DOI：
10.1371/journal.ppat.1010710
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发表时间：
2022-07
期刊：
影响因子：
6.7
通讯作者：
中科院分区：
文献类型：
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作者：
猪链球菌（Streptococcus suis，S.是引起猪和人类细菌性脑膜炎的重要病原体之一。逃避宿主的免疫防御和穿透血脑屏障（BBB）是S。猪是引起脑膜炎，而在这些致病过程中的潜在机制还没有完全理解。本研究通过检测小鼠脑膜炎模型红细胞、白色细胞计数、IL-8表达以及脑组织病理损伤，确定了一种富含丝氨酸重复序列（SRR）的糖蛋白SssP 1是脑膜炎发病过程中的关键促进因子。SssP 1被输出组装成菌毛样成分，从而促进细菌粘附和侵入人脑微血管内皮细胞（HBMEC），并在脑膜炎时激活宿主的炎症反应，但不参与肌动蛋白细胞骨架重排和紧密连接的破坏。此外，sssP 1的缺失显著减弱了S. suis在体内和体外穿过血脑屏障。下拉分析确定波形蛋白为脑膜炎期间SssP 1的潜在受体，并且随后的Far-Western印迹结果证实了由SssP 1的NR 2（第二非重复区域）区域介导的这种配体-受体结合。vimentin和S.激光共聚焦显微镜观察到波形蛋白显著增强SssP 1与血脑屏障的相互作用。进一步的研究发现，SssP 1的NR 216 -781和NR 1711 -2214片段依赖于波形蛋白的唾液酸化而与血脑屏障结合，当NR 216 -781或NR 1711 -2214的抗血清阻断细菌细胞或波形蛋白抗体阻断血脑屏障时，这种结合被显著减弱。当细菌细胞与波形蛋白预孵育时，或BBB与重组蛋白NR 216 -781、NR 1711 -2214或唾液酸酶预孵育时，观察到类似的结合减弱。总之，这些结果揭示了一种新的受体-配体相互作用，增强了粘附和穿透血脑屏障，导致细菌性脑膜炎的S。猪感染并强调波形蛋白在宿主与病原体相互作用中的重要性。猪链球菌（Streptococcus suis，S.猪）被认为是一种重要的人畜共患病原体，能够引起人类脑膜炎。穿透血脑屏障（BBB）是S.猪是引起脑膜炎，但其潜在的机制是不完全了解。在这里，我们确定了一个以前未表征的致病机制与S。由细菌SRR糖蛋白和宿主细胞骨架组分之间的相互作用介导的猪脑膜炎。在细菌感染期间，SRR蛋白SssP 1被输出以组装菌毛样组分，其依赖于波形蛋白的唾液酸化而驱动与BBB的强结合作用。这种相互作用有助于细菌粘附和穿透血脑屏障，并在脑膜炎期间诱导强烈的炎症反应。这一总体观察结果强调了宿主细胞表面波形蛋白相互作用在微生物发病机制中的重要性，并显着提高了我们对脑膜炎期间宿主屏障渗透的理解。
Streptococcus suis (S. suis) is one of the important pathogens that cause bacterial meningitis in pigs and humans. Evading host immune defences and penetrating the blood-brain barrier (BBB) are the preconditions for S. suis to cause meningitis, while the underlying mechanisms during these pathogenic processes are not fully understood. By detecting the red blood and white blood cells counts, IL-8 expression, and the pathological injury of brain in a mouse infection model, a serine-rich repeat (SRR) glycoprotein, designated as SssP1, was identified as a critical facilitator in the process of causing meningitis in this study. SssP1 was exported to assemble a fimbria-like component, thus contributed to the bacterial adhesion to and invasion into human brain microvascular endothelial cells (HBMECs), and activates the host inflammatory response during meningitis but is not involved in the actin cytoskeleton rearrangement and the disruption of tight junctions. Furthermore, the deletion of sssP1 significantly attenuates the ability of S. suis to traverse the BBB in vivo and in vitro. A pull-down analysis identified vimentin as the potential receptors of SssP1 during meningitis and following Far-Western blot results confirmed this ligand-receptor binding mediated by the NR2 (the second nonrepeat region) region of SssP1. The co-localisation of vimentin and S. suis observed by laser scanning confocal microscopy with multiplex fluorescence indicated that vimentin significantly enhances the interaction between SssP1 and BBB. Further study identified that the NR216-781 and NR1711-2214 fragments of SssP1 play critical roles to bind to the BBB depending on the sialylation of vimentin, and this binding is significantly attenuated when the antiserum of NR216-781 or NR1711-2214 blocked the bacterial cells, or the vimentin antibody blocked the BBB. Similar binding attenuations are observed when the bacterial cells were preincubated with the vimentin, or the BBB was preincubated with the recombinant protein NR216-781, NR1711-2214 or sialidase. In conclusion, these results reveal a novel receptor-ligand interaction that enhances adhesion to and penetration of the BBB to cause bacterial meningitis in the S. suis infection and highlight the importance of vimentin in host-pathogen interactions. Streptococcus suis (S. suis) is considered an important zoonotic pathogen capable of causing meningitis in humans. Penetrating the blood-brain barrier (BBB) is one of the preconditions for S. suis to cause meningitis, while its underlying mechanism is incompletely understood. Here we identified a previously uncharacterised pathogenic mechanism associated with S. suis meningitis mediated by the interaction between bacterial SRR glycoproteins and a host cytoskeletal component. During the bacterial infection, SRR protein SssP1 is exported to assemble a fimbria-like component, which drives a strong binding effect with the BBB depending on the sialylation of vimentin. This interaction contributes to the bacterial adhesion to and penetration of the BBB and induces a robust inflammatory response during meningitis. This overall observation underscores the significance of host cell surface vimentin interactions in microbial pathogenesis and markedly improves our understanding of host barrier penetration during meningitis.
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DOI：
10.1038/nrmicro1952
发表时间：
2008-08
期刊：
Nature reviews. Microbiology
影响因子：
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12.7
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10.1084/jem.20161668
发表时间：
2017-06-05
期刊：
The Journal of experimental medicine
影响因子：
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Henriques-Normark B